LCK (lymphocyte-specific protein tyrosine kinase, p56lck) is a Src-family non-receptor protein tyrosine kinase expressed mainly in T cells and NK cells. It is N-myristoylated and S-palmitoylated, which anchors it to the cytoplasmic face of the plasma membrane and to lipid rafts. Through a zinc clasp formed between its unique N-terminal region and the cytoplasmic tails of CD4 and CD8, LCK is coupled to the coreceptors and is brought to the T cell receptor (TCR)-CD3 complex when the TCR engages peptide-MHC. LCK initiates TCR signaling by phosphorylating the immunoreceptor tyrosine-based activation motifs (ITAMs) of CD3 and TCR zeta chains, which recruit ZAP70; LCK then phosphorylates and activates ZAP70 and also phosphorylates LAT and other substrates, with its SH2 domain binding phosphorylated ZAP70. Its activity is set by the balance of CSK-mediated phosphorylation of the inhibitory C-terminal Tyr505 and CD45 (PTPRC)-mediated dephosphorylation, together with activation-loop Tyr394 autophosphorylation that is reversed by phosphatases such as PTPN22 and DUSP22. LCK signaling is essential for pre-TCR and TCR-driven thymocyte development and mature T cell activation, and LCK also phosphorylates ITAMs of other receptors, such as the Fc gamma RIIIA zeta subunit in NK cells, and costimulatory receptor tails such as CD28. Selective recognition of TCR ITAMs is an intrinsic property of the LCK kinase domain, since grafting the LCK catalytic domain onto c-Src confers ITAM phosphorylation in T cells, and coreceptor-free LCK carries more Tyr394 phosphorylation and higher kinase activity than the CD4/CD8-bound pool. In humans, a homozygous hypomorphic LCK variant (P440S) causes T cell lymphopenia and combined immunodeficiency with intestinal inflammation, reflecting defective thymic development and loss of regulatory T cells.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000242 pericentriolar material | IDA PMID:7513706 Distinct intracellular localization of Lck and Fyn protein t... | KEEP AS NON CORE | Summary: Immunofluorescence in human T cells showed Lck at the plasma membrane and on pericentrosomal vesicles that co-localize with the mannose 6-phosphate receptor. Reason: The observed pericentrosomal signal is vesicular (endosomal/M6PR compartment) rather than a centrosome structural component; the principal site of LCK action is the cytoplasmic face of the plasma membrane. Retained as a minor, experimentally observed localization. Supporting Evidence: PMID:7513706 Lck was present at the plasma membrane, consistent with its proposed role in transmembrane signalling, and was also associated with pericentrosomal vesicles which co-localized with the cation-independent mannose 6-phosphate receptor. |
| GO:0001772 immunological synapse | IDA PMID:20007709 SOCS-6 negatively regulates T cell activation through target... | ACCEPT | Summary: Active LCK co-localizes with SOCS-6 at the immunological synapse after APC-T cell conjugation. Reason: LCK is recruited to the T cell side of the immunological synapse where it phosphorylates TCR-CD3 ITAMs; a physiologically relevant location for its core activity. Supporting Evidence: PMID:20007709 Confocal microscopy showed that upon APC-T cell conjugation, SOCS-6 was recruited to the immunological synapse and colocalized with the active form of p56(lck). |
| GO:0001784 phosphotyrosine residue binding | IPI PMID:20624904 Tarp regulates early Chlamydia-induced host cell survival th... | ACCEPT | Summary: LCK SH2 domain binds phosphotyrosine peptides (here from the Chlamydia effector Tarp on a human SH2 domain array). Reason: The LCK SH2 domain is a bona fide phosphotyrosine-binding module; it binds phosphorylated ZAP70 Tyr319 and Syk Tyr518/519, supporting kinase activation in TCR signaling. The term is informative and correct for LCK. Supporting Evidence: PMID:10318843 We show that a phosphopeptide encompassing the motif harboring Tyr319, YSDP, interacted with LckSH2, although with a lower affinity compared with a phosphopeptide containing the optimal binding motif, YEEI. PMID:8798676 The SH2 domain of Lck bound the autophosphorylation site only when both Tyr518 and Tyr519 were phosphorylated. |
| GO:0002429 immune response-activating cell surface receptor signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA-predicted involvement in immune response-activating cell surface receptor signaling. Reason: Correct general parent of T cell receptor and Fc receptor signaling pathways in which LCK phosphorylates ITAMs; the more specific GO:0050852 is also annotated. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based protein kinase activity. Reason: Correct but general; LCK is a tyrosine-specific kinase (GO:0004713/GO:0004715 annotated separately). Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:12923167 Tyrosyl phosphorylation of Shp2 is required for normal ERK a... | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). The cached abstract of this reference concerns other tyrosine kinase systems and does not name LCK; the assertion is deferred to the curator because LCK tyrosine kinase activity is unambiguous. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:1381360 Steel factor stimulates the tyrosine phosphorylation of the ... | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). The cached abstract of this reference concerns other tyrosine kinase systems and does not name LCK; the assertion is deferred to the curator because LCK tyrosine kinase activity is unambiguous. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:18697750 Gab2 is involved in differential phosphoinositide 3-kinase s... | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). The cached abstract of this reference concerns other tyrosine kinase systems and does not name LCK; the assertion is deferred to the curator because LCK tyrosine kinase activity is unambiguous. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:9799234 Kit signaling through PI 3-kinase and Src kinase pathways: a... | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). The cached abstract of this reference concerns other tyrosine kinase systems and does not name LCK; the assertion is deferred to the curator because LCK tyrosine kinase activity is unambiguous. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:214242 Evidence that the transforming gene of avian sarcoma virus e... | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). The cached abstract of this reference concerns other tyrosine kinase systems and does not name LCK; the assertion is deferred to the curator because LCK tyrosine kinase activity is unambiguous. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:2470098 The CD4 and CD8 antigens are coupled to a protein-tyrosine k... | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:40592325 Proximity between LAG-3 and the T cell receptor guides suppr... | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:8478617 Physical and functional association of p56lck with Fc gamma ... | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | IMP PMID:8681956 Phosphorylated T cell receptor zeta-chain and ZAP70 tandem S... | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-1433506 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reactome places LCK as the catalyst in this event; the molecular function is correct irrespective of pathway context. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-1472121 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reactome places LCK as the catalyst in this event; the molecular function is correct irrespective of pathway context. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-202165 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reactome places LCK as the catalyst in this event; the molecular function is correct irrespective of pathway context. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-202291 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reactome places LCK as the catalyst in this event; the molecular function is correct irrespective of pathway context. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-210291 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reactome places LCK as the catalyst in this event; the molecular function is correct irrespective of pathway context. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-2395801 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reactome places LCK as the catalyst in this event; the molecular function is correct irrespective of pathway context. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-2396594 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reactome places LCK as the catalyst in this event; the molecular function is correct irrespective of pathway context. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-2424484 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reactome places LCK as the catalyst in this event; the molecular function is correct irrespective of pathway context. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-2424486 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reactome places LCK as the catalyst in this event; the molecular function is correct irrespective of pathway context. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-388831 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reactome places LCK as the catalyst in this event; the molecular function is correct irrespective of pathway context. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-388833 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reactome places LCK as the catalyst in this event; the molecular function is correct irrespective of pathway context. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-389762 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reactome places LCK as the catalyst in this event; the molecular function is correct irrespective of pathway context. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-434836 | ACCEPT | Summary: LCK catalyses ATP-dependent phosphorylation of tyrosine residues on protein substrates (CD3/zeta ITAMs, ZAP70, LAT and others). Reactome places LCK as the catalyst in this event; the molecular function is correct irrespective of pathway context. Reason: Protein tyrosine kinase activity is the core molecular function of LCK (EC 2.7.10.2), demonstrated with CD3 chains, TCR zeta, ZAP70 and LAT as substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Non-membrane spanning (cytoplasmic) protein tyrosine kinase activity of LCK. Reason: Most precise description of the core catalytic activity: LCK is a Src-family, lipid-anchored cytoplasmic tyrosine kinase that phosphorylates ITAMs, ZAP70 and other substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:16339550 Phosphorylation of Tyr315 and Zap70 association with CrkII were both dependent upon the Lck protein tyrosine kinase. PMID:16938345 Further, the in vitro kinase assay using purified Lck and LAT shows that Lck directly phosphorylates LAT. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IDA PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | ACCEPT | Summary: Non-membrane spanning (cytoplasmic) protein tyrosine kinase activity of LCK. Reason: Most precise description of the core catalytic activity: LCK is a Src-family, lipid-anchored cytoplasmic tyrosine kinase that phosphorylates ITAMs, ZAP70 and other substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:16339550 Phosphorylation of Tyr315 and Zap70 association with CrkII were both dependent upon the Lck protein tyrosine kinase. PMID:16938345 Further, the in vitro kinase assay using purified Lck and LAT shows that Lck directly phosphorylates LAT. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IDA PMID:16339550 T cell activation-induced CrkII binding to the Zap70 protein... | ACCEPT | Summary: Non-membrane spanning (cytoplasmic) protein tyrosine kinase activity of LCK. Reason: Most precise description of the core catalytic activity: LCK is a Src-family, lipid-anchored cytoplasmic tyrosine kinase that phosphorylates ITAMs, ZAP70 and other substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:16339550 Phosphorylation of Tyr315 and Zap70 association with CrkII were both dependent upon the Lck protein tyrosine kinase. PMID:16938345 Further, the in vitro kinase assay using purified Lck and LAT shows that Lck directly phosphorylates LAT. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IDA PMID:38614099 ITPRIPL1 binds CD3Ξ΅ to impede TΒ cell activation and enable t... | ACCEPT | Summary: Non-membrane spanning (cytoplasmic) protein tyrosine kinase activity of LCK. Reason: Most precise description of the core catalytic activity: LCK is a Src-family, lipid-anchored cytoplasmic tyrosine kinase that phosphorylates ITAMs, ZAP70 and other substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:16339550 Phosphorylation of Tyr315 and Zap70 association with CrkII were both dependent upon the Lck protein tyrosine kinase. PMID:16938345 Further, the in vitro kinase assay using purified Lck and LAT shows that Lck directly phosphorylates LAT. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IDA PMID:8681956 Phosphorylated T cell receptor zeta-chain and ZAP70 tandem S... | ACCEPT | Summary: Non-membrane spanning (cytoplasmic) protein tyrosine kinase activity of LCK. Reason: Most precise description of the core catalytic activity: LCK is a Src-family, lipid-anchored cytoplasmic tyrosine kinase that phosphorylates ITAMs, ZAP70 and other substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:16339550 Phosphorylation of Tyr315 and Zap70 association with CrkII were both dependent upon the Lck protein tyrosine kinase. PMID:16938345 Further, the in vitro kinase assay using purified Lck and LAT shows that Lck directly phosphorylates LAT. |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IEA GO_REF:0000003 | ACCEPT | Summary: Non-membrane spanning (cytoplasmic) protein tyrosine kinase activity of LCK. Reason: Most precise description of the core catalytic activity: LCK is a Src-family, lipid-anchored cytoplasmic tyrosine kinase that phosphorylates ITAMs, ZAP70 and other substrates. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:16339550 Phosphorylation of Tyr315 and Zap70 association with CrkII were both dependent upon the Lck protein tyrosine kinase. PMID:16938345 Further, the in vitro kinase assay using purified Lck and LAT shows that Lck directly phosphorylates LAT. |
| GO:0004722 protein serine/threonine phosphatase activity | IDA PMID:8506364 Phosphorylation of Ser-42 and Ser-59 in the N-terminal regio... | REMOVE | Summary: The cited study maps phorbol-ester-induced serine phosphorylation sites (Ser-42, Ser-59) on Lck and the kinases that phosphorylate them. Reason: The paper reports LCK as a substrate of serine/threonine kinases (MAPK, PKA, PKC), not as a phosphatase. LCK has no phosphatase domain; the annotation appears to invert the direction of the reaction and is contradicted by the evidence itself. Supporting Evidence: PMID:8506364 In vitro kinase assays show that Ser-59 can be uniquely phosphorylated by mitogen-activated protein kinase and that Ser-42 can be phosphorylated by either protein kinase A or protein kinase C. |
| GO:0005102 signaling receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for signaling receptor binding (Src-family node). Reason: LCK binds the cytoplasmic tails of signaling receptors (CD4, CD8, CD2, IL2RB) and this is inherited across the Src family; specific CD4/CD8 receptor binding terms are also present. Supporting Evidence: PMID:2470098 In this study, we reveal that the human CD8 antigen is also associated with the T-cell-specific protein-tyrosine kinase (p56lck). |
| GO:0005515 protein binding | IPI PMID:10209036 SHP2-interacting transmembrane adaptor protein (SIT), a nove... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:10318843 Tyrosine 319 in the interdomain B of ZAP-70 is a binding sit... | MODIFY | Summary: The LCK SH2 domain binds phosphorylated ZAP-70 Tyr319. Reason: Generic protein binding is uninformative; the study directly supports a more informative molecular function for LCK. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:10318843 We show that a phosphopeptide encompassing the motif harboring Tyr319, YSDP, interacted with LckSH2, although with a lower affinity compared with a phosphopeptide containing the optimal binding motif, YEEI. |
| GO:0005515 protein binding | IPI PMID:10369126 Galectin-1, a natural ligand for the receptor-type protein t... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:10553045 Lad, an adapter protein interacting with the SH2 domain of p... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:10656681 Self-association of the SET domains of human ALL-1 and of Dr... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:11278465 The tyrosine kinase Hck is an inhibitor of HIV-1 replication... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:11741929 Phosphorylation-dependent interactions between ADAM15 cytopl... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:11978774 BY55/CD160 acts as a co-receptor in TCR signal transduction ... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:14625311 Subdomain X of the kinase domain of Lck binds CD45 and facil... | MODIFY | Summary: CD45 phosphatase domains bind the LCK kinase domain, SH2 domain and unique region. Reason: Generic protein binding is uninformative; the study directly supports a more informative molecular function for LCK. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:14625311 Analysis of the interaction between the cytoplasmic domain of CD45 and its substrate, Lck, revealed that the active, membrane-proximal phosphatase domain of CD45 (CD45-D1) bound to the phosphorylated Lck kinase domain, the SH2 domain, and the unique N-terminal region of Lck. |
| GO:0005515 protein binding | IPI PMID:14757743 Unc119, a novel activator of Lck/Fyn, is essential for T cel... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:15536084 Molecular basis for a direct interaction between the Syk pro... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:15554700 Characterization of Lck-binding elements in the herpesviral ... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:15827961 The C terminus of T cell-specific adapter protein (TSAd) is ... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16051843 Tyrosine phosphorylation of the Tio oncoprotein is essential... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16099425 Regulation of Bcl-3 through interaction with the Lck tyrosin... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16107303 A rare mRNA variant of the human lymphocyte-specific protein... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16195219 Inhibition of SRC tyrosine kinases suppresses activation of ... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16245368 Molecular basis for regulation of Src by the docking protein... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16245368 Molecular basis for regulation of Src by the docking protein... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16461343 Identification of substrates of human protein-tyrosine phosp... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16461343 Identification of substrates of human protein-tyrosine phosp... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16839418 Structure function analysis of SH2D2A isoforms expressed in ... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16888650 Glucocorticoids cause rapid dissociation of a T-cell-recepto... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16888650 Glucocorticoids cause rapid dissociation of a T-cell-recepto... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16888650 Glucocorticoids cause rapid dissociation of a T-cell-recepto... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16888650 Glucocorticoids cause rapid dissociation of a T-cell-recepto... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16899217 Magicin associates with the Src-family kinases and is phosph... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:16938345 Evidence of LAT as a dual substrate for Lck and Syk in T lym... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:17005671 Growth transformation of human T cells by herpesvirus saimir... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:17005671 Growth transformation of human T cells by herpesvirus saimir... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:17382937 A proline to glycine mutation in the Lck SH3-domain affects ... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:18424730 Carcinoembryonic antigen-related cell adhesion molecule 1 in... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:18539162 Distinct interactions between ubiquitin and the SH3 domains ... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:19167335 Large-scale structural analysis of the classical human prote... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:19167335 Large-scale structural analysis of the classical human prote... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:19167335 Large-scale structural analysis of the classical human prote... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:19192391 PKD2 interacts with Lck and regulates NFAT activity in T cel... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:20100835 Src kinase phosphorylates RUNX3 at tyrosine residues and loc... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:21719704 Substrate specificity of lymphoid-specific tyrosine phosphat... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:21964608 A motif in the V3 domain of the kinase PKC-ΞΈ determines its ... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:22939624 Quantitative analysis of HSP90-client interactions reveals p... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:23460737 GRB2-mediated recruitment of THEMIS to LAT is essential for ... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:25036101 Identification of SH3 domain proteins interacting with the c... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:25825872 Preferred SH3 domain partners of ADAM metalloproteases inclu... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:27335501 ARAP, a Novel Adaptor Protein, Is Required for TCR Signaling... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:27335501 ARAP, a Novel Adaptor Protein, Is Required for TCR Signaling... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through ... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:7507203 Tyrosine phosphorylation of CD45 phosphotyrosine phosphatase... | MODIFY | Summary: Csk-phosphorylated CD45 binds the LCK SH2 domain. Reason: Generic protein binding is uninformative; the study directly supports a more informative molecular function for LCK. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:7507203 Tyrosine-phosphorylated CD45 bound p56lck through the SH2 domain of the kinase. |
| GO:0005515 protein binding | IPI PMID:7513706 Distinct intracellular localization of Lck and Fyn protein t... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:7852312 p70 phosphorylation and binding to p56lck is an early event ... | MODIFY | Summary: Tyrosine-phosphorylated p70 binds the LCK SH2 domain after IL-2 stimulation. Reason: Generic protein binding is uninformative; the study directly supports a more informative molecular function for LCK. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:7852312 In peripheral blood lymphocytes, we have observed an interleukin-2-dependent tyrosine phosphorylation of a 70-kDa protein and binding of tyrosine phosphorylated p70 to the SH2 domain of p56lck. |
| GO:0005515 protein binding | IPI PMID:7852312 p70 phosphorylation and binding to p56lck is an early event ... | MODIFY | Summary: Tyrosine-phosphorylated p70 binds the LCK SH2 domain after IL-2 stimulation. Reason: Generic protein binding is uninformative; the study directly supports a more informative molecular function for LCK. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:7852312 In peripheral blood lymphocytes, we have observed an interleukin-2-dependent tyrosine phosphorylation of a 70-kDa protein and binding of tyrosine phosphorylated p70 to the SH2 domain of p56lck. |
| GO:0005515 protein binding | IPI PMID:8114715 Lck-dependent tyrosyl phosphorylation of the phosphotyrosine... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:8576115 Demonstration of a direct interaction between p56lck and the... | MODIFY | Summary: LCK binds the CD45 cytoplasmic domain directly in vitro. Reason: Generic protein binding is uninformative; the study directly supports a more informative molecular function for LCK. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:8576115 In this study, recombinant purified p56lck was found to specifically associate with recombinant CD45 cytoplasmic domain protein, but not to the cytoplasmic domain of another related tyrosine phosphatase, receptor protein-tyrosine phosphatase alpha. |
| GO:0005515 protein binding | IPI PMID:8650207 Molecular cloning of a phosphotyrosine-independent ligand of... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:8798676 Identification of the site in the Syk protein tyrosine kinas... | MODIFY | Summary: The LCK SH2 domain binds doubly phosphorylated Syk Tyr518/Tyr519. Reason: Generic protein binding is uninformative; the study directly supports a more informative molecular function for LCK. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:8798676 The SH2 domain of Lck bound the autophosphorylation site only when both Tyr518 and Tyr519 were phosphorylated. |
| GO:0005515 protein binding | IPI PMID:9045636 Interaction between Sam68 and Src family tyrosine kinases, F... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:9175835 Tap: a novel cellular protein that interacts with tip of her... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005515 protein binding | IPI PMID:9341123 Human homologue of the Drosophila discs large tumor suppress... | REMOVE | Summary: IPI protein binding (interaction partner reported in this study). Reason: Generic protein binding is uninformative about LCK function. Removal does not dispute the reported interaction; where relevant, the interaction reflects LCK kinase-substrate or SH2/SH3-mediated contacts already captured by kinase activity and phosphotyrosine binding terms. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding inferred from the kinase domain. Reason: Required cofactor binding for the catalytic tyrosine kinase activity. |
| GO:0005737 cytoplasm | IDA PMID:38614099 ITPRIPL1 binds CD3Ξ΅ to impede TΒ cell activation and enable t... | ACCEPT | Summary: LCK detected in the cytoplasm. Reason: Broad but correct: LCK is a cytoplasmic-face, lipid-anchored kinase. More specific plasma membrane terms are annotated. |
| GO:0005829 cytosol | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. Supporting Evidence: PMID:22034844 Dual N-terminal acylation of Lck with myristate (N-acylation) and palmitate (S-acylation) is essential for its membrane association and function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433418 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433428 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433451 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433454 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433456 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433488 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433506 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433514 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433542 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1470009 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1470010 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1470012 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1472121 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1562641 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-167566 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-200954 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202165 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202168 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202174 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202214 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202216 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202233 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202245 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202248 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202291 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202307 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202344 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205234 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205238 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205244 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205319 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-210289 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-210291 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2316434 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2395412 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2395801 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2396594 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2400009 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424480 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424482 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424484 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424486 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2424487 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-388814 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-388829 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-388831 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-388832 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-388833 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-389158 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-389348 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-389350 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-389352 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-389354 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-389381 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-389758 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-389759 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-389762 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-434836 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8852200 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8855381 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9018758 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9670412 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9670413 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9670414 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9670416 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9670417 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9670418 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9670426 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9706312 | KEEP AS NON CORE | Summary: Cytosol location (Reactome compartment convention / automated). Reason: LCK is synthesized as a soluble cytosolic protein before N-myristoylation and S-palmitoylation direct it to membranes; its functional pool acts at the cytoplasmic face of the plasma membrane. Reactome uses cytosol for membrane-peripheral reactions, so this location is acceptable but not the principal site of action. |
| GO:0005886 plasma membrane | EXP PMID:22034844 DHHC2 is a protein S-acyltransferase for Lck. | ACCEPT | Summary: LCK is anchored at the inner leaflet of the plasma membrane via dual N-terminal acylation. Reason: Plasma membrane is the principal site of LCK function, where it associates with CD4/CD8 and phosphorylates TCR-CD3 ITAMs. Supporting Evidence: PMID:22034844 Dual N-terminal acylation of Lck with myristate (N-acylation) and palmitate (S-acylation) is essential for its membrane association and function. PMID:7513706 Lck was present at the plasma membrane, consistent with its proposed role in transmembrane signalling, and was also associated with pericentrosomal vesicles which co-localized with the cation-independent mannose 6-phosphate receptor. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: LCK is anchored at the inner leaflet of the plasma membrane via dual N-terminal acylation. Reason: Plasma membrane is the principal site of LCK function, where it associates with CD4/CD8 and phosphorylates TCR-CD3 ITAMs. Supporting Evidence: PMID:22034844 Dual N-terminal acylation of Lck with myristate (N-acylation) and palmitate (S-acylation) is essential for its membrane association and function. PMID:7513706 Lck was present at the plasma membrane, consistent with its proposed role in transmembrane signalling, and was also associated with pericentrosomal vesicles which co-localized with the cation-independent mannose 6-phosphate receptor. |
| GO:0005886 plasma membrane | IDA PMID:12150984 Calpain II colocalizes with detergent-insoluble rafts on hum... | ACCEPT | Summary: LCK is anchored at the inner leaflet of the plasma membrane via dual N-terminal acylation. Reason: Plasma membrane is the principal site of LCK function, where it associates with CD4/CD8 and phosphorylates TCR-CD3 ITAMs. Supporting Evidence: PMID:22034844 Dual N-terminal acylation of Lck with myristate (N-acylation) and palmitate (S-acylation) is essential for its membrane association and function. PMID:7513706 Lck was present at the plasma membrane, consistent with its proposed role in transmembrane signalling, and was also associated with pericentrosomal vesicles which co-localized with the cation-independent mannose 6-phosphate receptor. |
| GO:0005886 plasma membrane | IDA PMID:12218089 Cutting edge: Fyn is essential for tyrosine phosphorylation ... | ACCEPT | Summary: LCK is anchored at the inner leaflet of the plasma membrane via dual N-terminal acylation. Reason: Plasma membrane is the principal site of LCK function, where it associates with CD4/CD8 and phosphorylates TCR-CD3 ITAMs. Supporting Evidence: PMID:22034844 Dual N-terminal acylation of Lck with myristate (N-acylation) and palmitate (S-acylation) is essential for its membrane association and function. PMID:7513706 Lck was present at the plasma membrane, consistent with its proposed role in transmembrane signalling, and was also associated with pericentrosomal vesicles which co-localized with the cation-independent mannose 6-phosphate receptor. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: LCK is anchored at the inner leaflet of the plasma membrane via dual N-terminal acylation. Reason: Plasma membrane is the principal site of LCK function, where it associates with CD4/CD8 and phosphorylates TCR-CD3 ITAMs. Supporting Evidence: PMID:22034844 Dual N-terminal acylation of Lck with myristate (N-acylation) and palmitate (S-acylation) is essential for its membrane association and function. PMID:7513706 Lck was present at the plasma membrane, consistent with its proposed role in transmembrane signalling, and was also associated with pericentrosomal vesicles which co-localized with the cation-independent mannose 6-phosphate receptor. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202214 | ACCEPT | Summary: LCK is anchored at the inner leaflet of the plasma membrane via dual N-terminal acylation. Reason: Plasma membrane is the principal site of LCK function, where it associates with CD4/CD8 and phosphorylates TCR-CD3 ITAMs. Supporting Evidence: PMID:22034844 Dual N-terminal acylation of Lck with myristate (N-acylation) and palmitate (S-acylation) is essential for its membrane association and function. PMID:7513706 Lck was present at the plasma membrane, consistent with its proposed role in transmembrane signalling, and was also associated with pericentrosomal vesicles which co-localized with the cation-independent mannose 6-phosphate receptor. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202233 | ACCEPT | Summary: LCK is anchored at the inner leaflet of the plasma membrane via dual N-terminal acylation. Reason: Plasma membrane is the principal site of LCK function, where it associates with CD4/CD8 and phosphorylates TCR-CD3 ITAMs. Supporting Evidence: PMID:22034844 Dual N-terminal acylation of Lck with myristate (N-acylation) and palmitate (S-acylation) is essential for its membrane association and function. PMID:7513706 Lck was present at the plasma membrane, consistent with its proposed role in transmembrane signalling, and was also associated with pericentrosomal vesicles which co-localized with the cation-independent mannose 6-phosphate receptor. |
| GO:0005911 cell-cell junction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara projection of mouse Lck cell-cell junction location. Reason: Likely reflects LCK enrichment at T cell-APC contacts (immunological synapse); acceptable as a minor location, but the immunological synapse term is more precise. |
| GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA for cell surface receptor protein tyrosine kinase signaling pathway (Src-family node). Reason: Src-family kinases act downstream of receptor tyrosine kinases, and Reactome places LCK among Src kinases that phosphorylate KIT Tyr900. For LCK this is a minor context; its main receptors (TCR, CD4/CD8) lack intrinsic kinase activity. |
| GO:0009410 response to xenobiotic stimulus | IDA PMID:16116473 The tyrosine kinase Lck is a positive regulator of the mitoc... | MARK AS OVER ANNOTATED | Summary: Lck-deficient Jurkat T cells were resistant to anticancer drugs; re-expression restored apoptosis via Bak expression. Reason: The evidence shows LCK is necessary for Bak expression and drug-induced mitochondrial apoptosis, not that LCK performs a response to the drug. This is a downstream/indirect effect. Supporting Evidence: PMID:16116473 Expression of Bak was completely absent in Lck-deficient cells, while re-expression of Lck transcriptionally triggered Bak expression and conferred sensitivity to apoptosis, associated with a proapoptotic conformational change of Bak. |
| GO:0016004 phospholipase activator activity | IDA PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | UNDECIDED | Summary: Assigned from a study of PLCgamma2 tyrosine residues in B-cell signaling. Reason: The cached abstract discusses Btk and Syk as PLCgamma2 kinases and does not mention LCK; full text is not available. If LCK activates PLCgamma2 it would be by tyrosine phosphorylation, which is captured by protein tyrosine kinase activity rather than phospholipase activator activity. Cannot verify. |
| GO:0019901 protein kinase binding | IPI PMID:8618896 Phosphotyrosine-independent binding of a 62-kDa protein to t... | UNDECIDED | Summary: IPI with RASA1 (UniProtKB:P20936) from a study of a phosphotyrosine-independent 62-kDa ligand of the Lck SH2 domain. Reason: The abstract describes binding of p62 to the Lck SH2 domain regulated by Ser-59 phosphorylation; the WITH partner RASA1 is not a protein kinase, so the term may be mis-assigned, but full text is unavailable to verify. |
| GO:0019903 protein phosphatase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LCK associates with protein tyrosine phosphatases (CD45, PTPN2/TCPTP, DUSP22/JKAP, PTPN22) that dephosphorylate its regulatory tyrosines. Reason: Phosphatase binding reflects LCK acting as a phosphatase substrate during regulation of its activity (Y394/Y505), which is important for TCR signal tuning but is not the activity LCK performs. |
| GO:0019903 protein phosphatase binding | IPI PMID:22080863 T cell protein tyrosine phosphatase attenuates T cell signal... | KEEP AS NON CORE | Summary: LCK associates with protein tyrosine phosphatases (CD45, PTPN2/TCPTP, DUSP22/JKAP, PTPN22) that dephosphorylate its regulatory tyrosines. Reason: Phosphatase binding reflects LCK acting as a phosphatase substrate during regulation of its activity (Y394/Y505), which is important for TCR signal tuning but is not the activity LCK performs. Supporting Evidence: PMID:22080863 Active SFKs phosphorylate TCRΞΆ and CD3Ξ΅, allowing for the recruitment of the tyrosine kinase ZAP-70 (ΞΆ chainβassociated protein kinase of 70 kDa), which in turn is phosphorylated and activated by Lck to instigate effector cascades that promote gene expression, proliferation, and differentiation ( 1 β 3 ). |
| GO:0019903 protein phosphatase binding | IPI PMID:24714587 The phosphatase JKAP/DUSP22 inhibits T-cell receptor signall... | KEEP AS NON CORE | Summary: LCK associates with protein tyrosine phosphatases (CD45, PTPN2/TCPTP, DUSP22/JKAP, PTPN22) that dephosphorylate its regulatory tyrosines. Reason: Phosphatase binding reflects LCK acting as a phosphatase substrate during regulation of its activity (Y394/Y505), which is important for TCR signal tuning but is not the activity LCK performs. Supporting Evidence: PMID:24714587 Here we report that JKAP directly inactivates Lck by dephosphorylating tyrosine-394 residue during T-cell receptor (TCR) signalling. |
| GO:0030097 hemopoiesis | NAS PMID:12884910 Src family kinases in tumor progression and metastasis. | MARK AS OVER ANNOTATED | Summary: NAS from a review on Src family kinases in tumor progression. Reason: Hemopoiesis is far broader than LCK function; LCK acts in T cell (and some NK) lineage signaling, and the source is a cancer-focused review. |
| GO:0030168 platelet activation | TAS Reactome:R-HSA-76002 | MARK AS OVER ANNOTATED | Summary: Reactome platelet activation pathway. Reason: Platelet GPVI/FcR gamma ITAM signaling uses Src kinases such as FYN and LYN; LCK is a lymphoid kinase and is not a principal platelet kinase. Included only as a generic Src-family entity in the pathway. |
| GO:0030217 T cell differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA for T cell differentiation. Reason: LCK transmits pre-TCR and TCR signals that drive thymocyte selection, so it participates in differentiation through its signaling activity. The knockout phenotype establishes necessity; the direct process LCK executes is TCR signaling. Supporting Evidence: PMID:12614355 The src-family kinases p56lck (Lck) and p59fyn (Fyn) are expressed in T cells and are among the first signaling molecules to be activated downstream of the T cell receptor (TCR). |
| GO:0030217 T cell differentiation | IMP PMID:1579166 Profound block in thymocyte development in mice lacking p56l... | KEEP AS NON CORE | Summary: LCK is required for thymocyte development; Lck-null mice have a block at the double-positive stage. Reason: LCK transmits pre-TCR and TCR signals that drive thymocyte selection, so it participates in differentiation through its signaling activity. The knockout phenotype establishes necessity; the direct process LCK executes is TCR signaling. Supporting Evidence: PMID:1579166 Lck-deficient mice show a pronounced thymic atrophy, with a dramatic reduction in the double-positive (CD4+CD8+) thymocyte population. |
| GO:0031295 T cell costimulation | TAS Reactome:R-HSA-388841 | KEEP AS NON CORE | Summary: Reactome: LCK phosphorylates CD28 (and related co-receptor tails) during co-stimulation. Reason: LCK directly phosphorylates CD28 cytoplasmic tyrosines, so it participates in costimulatory signaling; this is a secondary pathway to its core TCR signaling role. |
| GO:0031295 T cell costimulation | TAS Reactome:R-HSA-389356 | KEEP AS NON CORE | Summary: Reactome: LCK phosphorylates CD28 (and related co-receptor tails) during co-stimulation. Reason: LCK directly phosphorylates CD28 cytoplasmic tyrosines, so it participates in costimulatory signaling; this is a secondary pathway to its core TCR signaling role. |
| GO:0034116 positive regulation of heterotypic cell-cell adhesion | IMP PMID:27400149 WNK1 kinase balances T cell adhesion versus migration in viv... | KEEP AS NON CORE | Summary: siRNA knockdown of LCK reduced T cell adhesion and conjugate formation. Reason: LCK promotes integrin-mediated adhesion indirectly through TCR-initiated inside-out signaling; the knockdown shows necessity rather than a direct role in adhesion. Supporting Evidence: PMID:27400149 In contrast, knockdown of LCK resulted in decreased adhesion. |
| GO:0035556 intracellular signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Intracellular signal transduction (generic). Reason: Correct but uninformative; LCK signals downstream of cell surface receptors (TCR, CD4/CD8, FcgammaRIIIA). GO:0050852 better describes the core process. |
| GO:0035556 intracellular signal transduction | IMP PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | KEEP AS NON CORE | Summary: Intracellular signal transduction (generic). Reason: Correct but uninformative; LCK signals downstream of cell surface receptors (TCR, CD4/CD8, FcgammaRIIIA). GO:0050852 better describes the core process. |
| GO:0038094 Fc-gamma receptor signaling pathway | IDA PMID:8478617 Physical and functional association of p56lck with Fc gamma ... | KEEP AS NON CORE | Summary: FcgammaRIIIA crosslinking activates LCK in NK cells; LCK associates with and phosphorylates the zeta subunit. Reason: Direct participation via ITAM phosphorylation in an NK-cell Fc receptor pathway; a real but secondary context relative to TCR signaling. Supporting Evidence: PMID:8478617 Our studies show that the zeta chain, the signal transducing subunit of Fc gamma RIIIA and of T cell receptor, associates with p56lck and, in NK cells, is a substrate for this kinase. |
| GO:0042110 T cell activation | IDA PMID:38354704 Signaling via a CD27-TRAF2-SHP-1 axis during naive TΒ cell ac... | KEEP AS NON CORE | Summary: T cell activation (assigned from a CD27 co-signaling study). Reason: LCK is essential for TCR-driven T cell activation, but T cell activation is a broad outcome downstream of the signaling LCK performs. Supporting Evidence: PMID:14757743 The first step in T cell receptor for antigen (TCR) signaling is the activation of the receptor-bound Src kinases, Lck and Fyn. |
| GO:0042169 SH2 domain binding | IPI PMID:8794306 Human immunodeficiency virus type 1 Nef binds directly to Lc... | REMOVE | Summary: IPI with HIV-1 Nef (UniProtKB:P03406). Reason: The study shows the Nef-Lck interaction is mediated by the Nef proline-rich repeat and the Lck SH3 domain. Nef has no SH2 domain, so LCK binding an SH2 domain is not what was observed; the interaction is a viral manipulation of LCK rather than an LCK function. Supporting Evidence: PMID:8794306 Binding and coprecipitation assays with short synthetic peptides corresponding to the proline-rich repeat sequence [(Pxx)4] of Nef and the SH2, SH3, or SH2 and SH3 domains of Lck revealed that the interaction between these two proteins is at least in part mediated by the proline repeat sequence of Nef and the SH3 domain of Lck. |
| GO:0042608 T cell receptor binding | IPI PMID:8681956 Phosphorylated T cell receptor zeta-chain and ZAP70 tandem S... | KEEP AS NON CORE | Summary: Recombinant LCK phosphorylated the TCR zeta chain in vitro. Reason: LCK engages the TCR-CD3 complex as substrate (and via CD3epsilon association), but the enzyme-substrate relation is better captured by kinase activity; retained as a non-core binding term. Supporting Evidence: PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. PMID:40592325 Mechanistically, LAG-3 forms condensate with TCR signaling component CD3Ξ΅ through its intracellular FSAL motif, disrupting CD3Ξ΅/lymphocyte-specific protein kinase (Lck) association. |
| GO:0042609 CD4 receptor binding | IEA GO_REF:0000107 | ACCEPT | Summary: LCK binds the cytoplasmic tail of CD4. Reason: Coreceptor coupling via a zinc clasp between the LCK unique region and the CD4 tail is a defining feature that brings LCK to the MHC-engaged TCR. Supporting Evidence: PMID:2470098 In this study, we reveal that the human CD8 antigen is also associated with the T-cell-specific protein-tyrosine kinase (p56lck). PMID:12732664 Coaggregation of TCR and CD4 leads to Lck activation within seconds outside lipid rafts, followed by its translocation into lipid rafts and the activation of colocalized Fyn. file:human/LCK/LCK-deep-research-falcon.md binding to the cytoplasmic tails of CD4 and CD8Ξ± coreceptors through cysteines 20 and 23 in a zinc-dependent manner |
| GO:0042609 CD4 receptor binding | IPI PMID:7486703 Interaction of p56lck with CD4 in the yeast two-hybrid syste... | ACCEPT | Summary: LCK binds the cytoplasmic tail of CD4. Reason: Coreceptor coupling via a zinc clasp between the LCK unique region and the CD4 tail is a defining feature that brings LCK to the MHC-engaged TCR. Supporting Evidence: PMID:2470098 In this study, we reveal that the human CD8 antigen is also associated with the T-cell-specific protein-tyrosine kinase (p56lck). PMID:12732664 Coaggregation of TCR and CD4 leads to Lck activation within seconds outside lipid rafts, followed by its translocation into lipid rafts and the activation of colocalized Fyn. |
| GO:0042610 CD8 receptor binding | IPI PMID:2470098 The CD4 and CD8 antigens are coupled to a protein-tyrosine k... | ACCEPT | Summary: LCK associates with the CD8 antigen in T cells. Reason: Constitutive association with CD8alpha tails couples LCK to MHC class I-restricted TCR engagement; a core coupling function. Supporting Evidence: PMID:2470098 In this study, we reveal that the human CD8 antigen is also associated with the T-cell-specific protein-tyrosine kinase (p56lck). |
| GO:0042802 identical protein binding | IPI PMID:17118402 Crystal structure analysis and solution studies of human Lck... | KEEP AS NON CORE | Summary: LCK self-association (zinc-induced SH3 dimerization; LCK-LCK interactions in reconstituted membranes). Reason: Homotypic LCK interactions may support trans-autophosphorylation, but the physiological significance is limited and not a core function. Supporting Evidence: PMID:17118402 Ultracentrifugation experiments confirm that in the presence of zinc ions, the Lck-SH3 domain also forms dimers in solution. |
| GO:0042802 identical protein binding | IPI PMID:24463463 In vitro membrane reconstitution of the T-cell receptor prox... | KEEP AS NON CORE | Summary: LCK self-association (zinc-induced SH3 dimerization; LCK-LCK interactions in reconstituted membranes). Reason: Homotypic LCK interactions may support trans-autophosphorylation, but the physiological significance is limited and not a core function. |
| GO:0043274 phospholipase binding | IPI PMID:11606584 Tyrosine residues in phospholipase Cgamma 2 essential for th... | UNDECIDED | Summary: Assigned from a study of PLCgamma2 in B-cell signaling. Reason: The cached abstract does not mention LCK and full text is unavailable; cannot verify the LCK-PLCgamma2 binding claim. |
| GO:0043548 phosphatidylinositol 3-kinase binding | IPI PMID:7504174 The SH3 domain of p56lck is involved in binding to phosphati... | KEEP AS NON CORE | Summary: The LCK SH3 domain binds phosphatidylinositol 3-kinase from T cell lysates. Reason: SH3-mediated recruitment of PI3K is an adaptor-like interaction that couples LCK to downstream signaling; real but not a core activity. Supporting Evidence: PMID:7504174 Deletions within the SH3 domain of p56lck abolished binding of PI3K activity from T-cell lysates, whereas deletion of the SH2 domain caused only a slight reduction in the level of PI3K activity bound to p56lck sequences. |
| GO:0045121 membrane raft | IDA PMID:12150984 Calpain II colocalizes with detergent-insoluble rafts on hum... | ACCEPT | Summary: LCK partitions into lipid rafts, and activated LCK translocates into rafts after TCR/CD4 co-aggregation. Reason: Acylated LCK is a well-established membrane raft component; raft translocation of activated LCK is important for activating Fyn. Supporting Evidence: PMID:12732664 Coaggregation of TCR and CD4 leads to Lck activation within seconds outside lipid rafts, followed by its translocation into lipid rafts and the activation of colocalized Fyn. |
| GO:0045121 membrane raft | IDA PMID:12732664 Regulation of Fyn through translocation of activated Lck int... | ACCEPT | Summary: LCK partitions into lipid rafts, and activated LCK translocates into rafts after TCR/CD4 co-aggregation. Reason: Acylated LCK is a well-established membrane raft component; raft translocation of activated LCK is important for activating Fyn. Supporting Evidence: PMID:12732664 Coaggregation of TCR and CD4 leads to Lck activation within seconds outside lipid rafts, followed by its translocation into lipid rafts and the activation of colocalized Fyn. |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:2470098 The CD4 and CD8 antigens are coupled to a protein-tyrosine k... | ACCEPT | Summary: LCK initiates TCR signaling by phosphorylating CD3/zeta ITAMs and ZAP70. Reason: Core biological process: LCK performs the first catalytic step of TCR signal transduction. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. PMID:8943371 Therefore, Lck functions in multiple manners in T-cell activation for the steps following ZAP-70 binding to ITAM. |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:38614099 ITPRIPL1 binds CD3Ξ΅ to impede TΒ cell activation and enable t... | ACCEPT | Summary: LCK initiates TCR signaling by phosphorylating CD3/zeta ITAMs and ZAP70. Reason: Core biological process: LCK performs the first catalytic step of TCR signal transduction. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. PMID:8943371 Therefore, Lck functions in multiple manners in T-cell activation for the steps following ZAP-70 binding to ITAM. |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:40592325 Proximity between LAG-3 and the T cell receptor guides suppr... | ACCEPT | Summary: LCK initiates TCR signaling by phosphorylating CD3/zeta ITAMs and ZAP70. Reason: Core biological process: LCK performs the first catalytic step of TCR signal transduction. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. PMID:8943371 Therefore, Lck functions in multiple manners in T-cell activation for the steps following ZAP-70 binding to ITAM. |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:8681956 Phosphorylated T cell receptor zeta-chain and ZAP70 tandem S... | ACCEPT | Summary: LCK initiates TCR signaling by phosphorylating CD3/zeta ITAMs and ZAP70. Reason: Core biological process: LCK performs the first catalytic step of TCR signal transduction. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. PMID:8943371 Therefore, Lck functions in multiple manners in T-cell activation for the steps following ZAP-70 binding to ITAM. |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:8943371 The kinase, SH3, and SH2 domains of Lck play critical roles ... | ACCEPT | Summary: LCK initiates TCR signaling by phosphorylating CD3/zeta ITAMs and ZAP70. Reason: Core biological process: LCK performs the first catalytic step of TCR signal transduction. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. PMID:8943371 Therefore, Lck functions in multiple manners in T-cell activation for the steps following ZAP-70 binding to ITAM. |
| GO:0050852 T cell receptor signaling pathway | TAS Reactome:R-HSA-202403 | ACCEPT | Summary: LCK initiates TCR signaling by phosphorylating CD3/zeta ITAMs and ZAP70. Reason: Core biological process: LCK performs the first catalytic step of TCR signal transduction. Supporting Evidence: PMID:2470098 Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. PMID:8681956 The protein tyrosine kinase (PTK) Lck phosphorylates the zeta-chain, which in turn associates with another PTK, ZAP70, and stimulates its phosphorylation activity. PMID:8943371 Therefore, Lck functions in multiple manners in T-cell activation for the steps following ZAP-70 binding to ITAM. |
| GO:0050853 B cell receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA for B cell receptor signaling pathway (Src-family node). Reason: Inherited from Src-family members active in B cells (LYN, BLK, FYN). LCK expression in B cells is limited; the function is plausible in some B cell subsets but is not a principal LCK role. |
| GO:0050862 positive regulation of T cell receptor signaling pathway | NAS PMID:12614355 The influence of the src-family kinases, Lck and Fyn, on T c... | MODIFY | Summary: NAS from a review on Lck and Fyn in T cell differentiation and activation. Reason: LCK is an integral catalytic component of TCR signaling rather than a regulator of it; the process should be T cell receptor signaling pathway. Proposed replacements: T cell receptor signaling pathway Supporting Evidence: PMID:12614355 The src-family kinases p56lck (Lck) and p59fyn (Fyn) are expressed in T cells and are among the first signaling molecules to be activated downstream of the T cell receptor (TCR). |
| GO:0050870 positive regulation of T cell activation | IDA PMID:8943371 The kinase, SH3, and SH2 domains of Lck play critical roles ... | KEEP AS NON CORE | Summary: Kinase, SH3 and SH2 domains of Lck are required for T cell activation by membrane-localized ZAP-70. Reason: Supports LCK participation in steps after ZAP-70 recruitment in TCR signaling; T cell activation is the downstream outcome. Supporting Evidence: PMID:8943371 Therefore, Lck functions in multiple manners in T-cell activation for the steps following ZAP-70 binding to ITAM. |
| GO:0050900 leukocyte migration | TAS Reactome:R-HSA-202733 | MARK AS OVER ANNOTATED | Summary: Reactome: cell surface interactions at the vascular wall. Reason: LCK appears in this Reactome pathway via receptor-proximal phosphorylation events (e.g., PECAM-1); leukocyte migration is not a process LCK executes. |
| GO:0051117 ATPase binding | IPI PMID:15671290 The influence of SRC-family tyrosine kinases on Na,K-ATPase ... | MARK AS OVER ANNOTATED | Summary: LCK tyrosine-phosphorylated Na,K-ATPase alpha1 in lens epithelium membranes in vitro without altering ATPase activity. Reason: In vitro kinase-substrate association in a tissue where LCK is not a physiological regulator; not informative for LCK biology. Supporting Evidence: PMID:15671290 Na,K-ATPase activity in membrane material treated with Lck or Fes was not significantly altered, even though Lck and Fes treatment induced robust tyrosine phosphorylation. |
| GO:0051132 NK T cell activation | IDA PMID:37006235 Galectin-9 promotes natural killer cells activity via intera... | MARK AS OVER ANNOTATED | Summary: Galectin-9/CD44 engagement increased phospho-LCK in mouse NK cells. Reason: LCK phosphorylation was only a readout in NK (not NK T) cells; LCK was not perturbed, so the study does not show that LCK carries out NK T cell activation. Supporting Evidence: PMID:37006235 Subsequently, this interaction resulted in enhanced expression of Phospho-LCK, ERK, Akt, MAPK, and mTOR in NK cells. |
| GO:0051209 release of sequestered calcium ion into cytosol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Release of sequestered calcium into cytosol (projected from rodent Lck). Reason: Calcium release is performed by IP3 receptors downstream of PLCgamma1 activation; LCK acts several steps upstream by initiating TCR signaling. Necessity, not participation. |
| GO:0051209 release of sequestered calcium ion into cytosol | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Release of sequestered calcium into cytosol (projected from rodent Lck). Reason: Calcium release is performed by IP3 receptors downstream of PLCgamma1 activation; LCK acts several steps upstream by initiating TCR signaling. Necessity, not participation. |
| GO:0051240 positive regulation of multicellular organismal process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA prediction of positive regulation of multicellular organismal process. Reason: Extremely general term that conveys no information about LCK function. |
| GO:0051249 regulation of lymphocyte activation | NAS PMID:7852312 p70 phosphorylation and binding to p56lck is an early event ... | KEEP AS NON CORE | Summary: NAS: p70 phosphorylation and binding to Lck in IL-2-induced T cell proliferation. Reason: LCK contributes to TCR- and IL-2R-linked signals that regulate lymphocyte activation; a downstream, non-core description. Supporting Evidence: PMID:7852312 In peripheral blood lymphocytes, we have observed an interleukin-2-dependent tyrosine phosphorylation of a 70-kDa protein and binding of tyrosine phosphorylated p70 to the SH2 domain of p56lck. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Detected in B cell-derived exosomes by proteomics (HDA). Reason: High-throughput detection; acylated membrane kinases are frequently captured in exosome preparations. Not a site of function. |
| GO:0160162 CD27 signaling pathway | IDA PMID:38354704 Signaling via a CD27-TRAF2-SHP-1 axis during naive TΒ cell ac... | UNDECIDED | Summary: Assigned from a study of CD27-TRAF2-SHP-1 signaling in naive CD8 T cells. Reason: The cached abstract does not mention LCK and full text is not available; cannot determine whether LCK performs a step of CD27 signaling or is a readout of TCR co-stimulation. |
| GO:1903039 positive regulation of leukocyte cell-cell adhesion | IMP PMID:27400149 WNK1 kinase balances T cell adhesion versus migration in viv... | KEEP AS NON CORE | Summary: siRNA knockdown of LCK reduced T cell adhesion and conjugate formation. Reason: LCK promotes integrin-mediated adhesion indirectly through TCR-initiated inside-out signaling; the knockdown shows necessity rather than a direct role in adhesion. Supporting Evidence: PMID:27400149 In contrast, knockdown of LCK resulted in decreased adhesion. |
| GO:1990405 protein antigen binding | IEA GO_REF:0000107 | REMOVE | Summary: Ensembl Compara projection of protein antigen binding from mouse Lck. Reason: LCK does not bind antigen; antigen recognition is performed by the TCR and MHC molecules. The projected term is biologically unfounded for LCK. |
| GO:2001244 positive regulation of intrinsic apoptotic signaling pathway | IMP PMID:16116473 The tyrosine kinase Lck is a positive regulator of the mitoc... | KEEP AS NON CORE | Summary: Lck re-expression restored Bak expression and drug-induced mitochondrial apoptosis in Lck-deficient Jurkat cells. Reason: LCK controls Bak transcription and thereby sensitises cells to intrinsic apoptosis; an indirect, context-specific role. Supporting Evidence: PMID:16116473 Expression of Bak was completely absent in Lck-deficient cells, while re-expression of Lck transcriptionally triggered Bak expression and conferred sensitivity to apoptosis, associated with a proapoptotic conformational change of Bak. |
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Download this section (compressed HTML)Q: What fraction of LCK is coreceptor-bound versus free in naive CD4 and CD8 T cells, and does the free pool dominate TCR ITAM phosphorylation for high-affinity ligands?
Q: Does LCK directly participate in CD27 or other TNFR-family co-signaling, or is LCK phosphorylation only a readout of concurrent TCR stimulation (PMID:38354704)?
Q: Is LCK a direct, physiologically relevant kinase for PLCgamma2 in B cells, as implied by the phospholipase annotations from PMID:11606584?
Q: Does ZAP70-mediated phosphorylation of LCK SH2-domain Tyr192, which reviews describe as reducing LCK association with CD45, operate as a physiological negative-feedback loop in primary human T cells, and which direct primary evidence supports it?
Q: Which residues in the LCK kinase domain (absent from c-Src) confer its intrinsic selectivity for TCR ITAMs (PMID:42638732), and do they also explain LCK preference for basic substrate contexts?
Q: Is there a functional nuclear pool of LCK in T cells or in LCK-expressing tumor cells, as claimed in recent reviews, and does it have substrates distinct from the plasma-membrane pool?
Experiment: Compare wild-type, kinase-dead (K273R) and CD4/CD8-binding-deficient (zinc clasp C20/C23A) LCK re-expressed in LCK-knockout human T cells stimulated with TCR plus trimeric CD70, reading out CD27 signaling and ITAM phosphorylation.
Hypothesis: LCK kinase activity, and not its scaffolding functions, is required for CD27-dependent memory gene programs in naive CD8 T cells.
Type: genetic complementation
Experiment: Building on whole kinase-domain swaps (PMID:42638732), introduce LCK-to-Src and Src-to-LCK point substitutions at residues lining the substrate-binding groove and measure CD3 zeta Y142 and ZAP70 Y319 phosphorylation in an SFK-deficient T cell line, alongside in vitro kinetics on ITAM peptides.
Hypothesis: A small set of kinase-domain residues that differ between LCK and c-Src determines LCK selectivity for TCR ITAMs.
Type: site-directed mutagenesis
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