Serine/threonine kinase STK11 that activates AMPK-family kinases and regulates polarity, growth, and energy stress responses.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: LKB1 is a serine/threonine protein kinase. Reason: UniProt catalytic activity indicates serine/threonine kinase function. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) file:genes/DROME/Lkb1/Lkb1-deep-research-falcon.md RecName: Full=Serine/threonine-protein kinase STK11 |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: LKB1 localizes to the cytoplasm. Reason: UniProt lists cytoplasmic localization. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}. |
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: LKB1 participates in intracellular signal transduction via AMPK-related kinases. Reason: Regulation of AMPK-family kinases places LKB1 in intracellular signaling pathways. Supporting Evidence: PMID:25996931 LKB1 plays important roles in governing energy homeostasis by regulating AMP-activated protein kinase (AMPK) and other AMPK-related kinases |
| GO:0000166 nucleotide binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: LKB1 binds nucleotides as part of its kinase reaction. Reason: The catalytic reaction uses ATP, indicating nucleotide binding. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0001558 regulation of cell growth | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: LKB1 regulates organ growth through apoptosis signaling. Reason: LKB1 negatively regulates organ growth via apoptosis. Supporting Evidence: PMID:16273080 Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: LKB1 has protein kinase activity. Reason: Catalytic activity confirms protein kinase function. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: LKB1 is a serine/threonine protein kinase. Reason: Lkb1 has a protein kinase domain carrying the PROSITE Ser/Thr kinase active-site signature, and fly genetics shows Drosophila LKB1 phosphorylates the activation-loop threonine (Thr196) of SIK3 in vivo (PMID:25996931, the source of the separate IMP row). Together these support Ser/Thr protein kinase activity for the fly protein. Supporting Evidence: PMID:25996931 Wild-type and kinase-dead (K70M) SIK3 were highly phosphorylated at Thr196 by LKB1 file:genes/DROME/Lkb1/Lkb1-uniprot.txt DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. file:genes/DROME/Lkb1/Lkb1-uniprot.txt DR Pfam; PF00069; Pkinase; 1. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: LKB1 uses ATP in its catalytic reaction. Reason: The kinase reaction explicitly consumes ATP. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: LKB1 can localize to the nucleus per UniProt annotation. Reason: UniProt lists nucleus as a subcellular location. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}. Nucleus |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: LKB1 localizes to the cytoplasm. Reason: UniProt lists cytoplasmic localization. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}. |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | MODIFY | Summary: LKB1 regulates apoptosis rather than being a core apoptotic machinery component. Reason: LKB1 induces apoptosis via JNK signaling; use positive regulation of apoptotic process. Proposed replacements: positive regulation of apoptotic process Supporting Evidence: PMID:16273080 Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis |
| GO:0006974 DNA damage response | IEA GO_REF:0000043 | UNDECIDED | Summary: DNA damage response is not supported by the accessible sources. Reason: No direct DNA damage response evidence was found in the available abstracts. Supporting Evidence: PMID:17507418 mutations disrupt spindle formation, resulting in frequent polyploid cells in larval brains |
| GO:0016301 kinase activity | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: LKB1 has kinase activity. Reason: Catalytic activity confirms kinase function. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: LKB1 is a transferase (kinase) enzyme. Reason: Kinases transfer phosphate groups from ATP. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0030010 establishment of cell polarity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: LKB1 is required for cell polarity establishment. Reason: Lkb1 is required for oocyte A-P polarity and epithelial polarity. Supporting Evidence: PMID:12540903 homologue, lkb1, is required for the early A-P polarity of the oocyte |
| GO:0030295 protein kinase activator activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: LKB1 activates AMPK and related kinases. Reason: LKB1 regulates AMPK and other AMPK-related kinases. Supporting Evidence: PMID:25996931 LKB1 plays important roles in governing energy homeostasis by regulating AMP-activated protein kinase (AMPK) and other AMPK-related kinases |
| GO:0042593 glucose homeostasis | IEA GO_REF:0000002 | UNDECIDED | Summary: Glucose homeostasis is not directly supported by the accessible evidence. Reason: Available sources focus on lipid metabolism and polarity rather than glucose homeostasis. Supporting Evidence: PMID:25996931 LKB1 mutants display decreased lipid storage and increased gene expression of brummer |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: LKB1 binds divalent metal ions required for catalysis. Reason: UniProt lists Mg2+ and Mn2+ as cofactors. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt Name=Mg(2+) file:genes/DROME/Lkb1/Lkb1-uniprot.txt Name=Mn(2+) |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ... | MODIFY | Summary: The cited study supports the opposite sign; LKB1 restrains cell proliferation through AMPK. Reason: The study (PMID:36899949) shows that PDK1 phosphorylation inhibits LKB1, decreasing activation of AMPK and its target mTOR, which leads to increased cell size and proliferation; conversely, overactivation of the LKB1-AMPK/mTOR axis reduces body size by decreasing cell proliferation. Active LKB1 therefore negatively regulates cell population proliferation, consistent with its tumour-suppressor role and with the same paper's TORC1 data (corrected here from positive to negative regulation of TORC1 signaling). The same row on AMPKalpha is modified to the same term. Proposed replacements: negative regulation of cell population proliferation Supporting Evidence: PMID:36899949 thus resulting in decreased activation of AMPK and its downstream target mTOR, which leads to increased cell size and proliferation PMID:36899949 adult flies exhibit a reduced body size due to decreased cell proliferation upon overactivation of the AMPK/mTOR axis PMID:16273080 Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ... | KEEP AS NON CORE | Summary: LKB1 association with membranes is noted in the PDK1 interaction study. Reason: PDK1-mediated regulation of LKB1 involves membrane-associated interactions. Supporting Evidence: PMID:36899949 phosphorylation of LKB1 by PDK1 results in an inhibition of LKB1, decreased activation of AMPK and enhanced cell growth |
| GO:0043539 protein serine/threonine kinase activator activity | IDA PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ... | KEEP AS NON CORE | Summary: LKB1 activates serine/threonine kinases such as AMPK/SIKs. Reason: LKB1 regulates AMPK and other AMPK-related kinases. Supporting Evidence: PMID:25996931 LKB1 plays important roles in governing energy homeostasis by regulating AMP-activated protein kinase (AMPK) and other AMPK-related kinases PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation and Organ Growth by Decreased Activation of AMPK. |
| GO:1904263 positive regulation of TORC1 signaling | IMP PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ... | MODIFY | Summary: Positive regulation of TORC1 signaling is inconsistent with LKB1βAMPK inhibition of mTOR. Reason: AMPK activation downstream of LKB1 inhibits mTOR; use negative regulation of TORC1 signaling instead. Proposed replacements: negative regulation of TORC1 signaling Supporting Evidence: PMID:36899949 Activation of AMPK by low energy supply and phosphorylation of LKB1 results in an inhibition of mTOR |
| GO:0007291 sperm individualization | IMP PMID:28767695 Drosophila LKB1 is required for the assembly of the polarize... | KEEP AS NON CORE | Summary: LKB1 is required for spermatid individualization. Reason: LKB1 is required for actin cone formation enabling spermatid individualization. Supporting Evidence: PMID:28767695 dLKB1 is required in the germline for the formation of the actin cone, the polarized structure that allows spermatid individualization |
| GO:0004674 protein serine/threonine kinase activity | IMP PMID:25996931 Feeding and Fasting Signals Converge on the LKB1-SIK3 Pathwa... | ACCEPT | Summary: LKB1 is a serine/threonine protein kinase. Reason: UniProt catalytic activity indicates serine/threonine kinase function. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) PMID:25996931 Feeding and Fasting Signals Converge on the LKB1-SIK3 Pathway to Regulate Lipid Metabolism in Drosophila. |
| GO:0010897 negative regulation of triglyceride catabolic process | IMP PMID:25996931 Feeding and Fasting Signals Converge on the LKB1-SIK3 Pathwa... | KEEP AS NON CORE | Summary: LKB1 suppresses lipolysis and supports lipid storage. Reason: LKB1 mutants show decreased lipid storage and increased lipase expression. Supporting Evidence: PMID:25996931 LKB1 mutants display decreased lipid storage and increased gene expression of brummer |
| GO:0005515 protein binding | IPI PMID:29084199 Class III phosphatidylinositol-3-OH kinase controls epitheli... | UNDECIDED | Summary: Protein binding evidence is not explicit in the available abstract for this annotation. Reason: The endosomal regulation study does not explicitly document LKB1 binding partners in the abstract. Supporting Evidence: PMID:29084199 dysregulation of endosomally localized Liver Kinase B1 (LKB1, also known as STK11) |
| GO:0005768 endosome | IDA PMID:29084199 Class III phosphatidylinositol-3-OH kinase controls epitheli... | KEEP AS NON CORE | Summary: LKB1 localizes to endosomes in epithelial cells. Reason: Endosomal LKB1 localization is reported in epithelial integrity studies. Supporting Evidence: PMID:29084199 dysregulation of endosomally localized Liver Kinase B1 (LKB1, also known as STK11) |
| GO:0005938 cell cortex | IDA PMID:29084199 Class III phosphatidylinositol-3-OH kinase controls epitheli... | KEEP AS NON CORE | Summary: LKB1 accumulates at the cell cortex. Reason: LKB1 overexpression leads to cortical accumulation. Supporting Evidence: PMID:18054329 Lkb1, which accumulates in the cell cortex PMID:29084199 Class III phosphatidylinositol-3-OH kinase controls epithelial integrity through endosomal LKB1 regulation. |
| GO:0004674 protein serine/threonine kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: LKB1 is a serine/threonine protein kinase. Reason: Lkb1 has a protein kinase domain carrying the PROSITE Ser/Thr kinase active-site signature, and fly genetics shows Drosophila LKB1 phosphorylates the activation-loop threonine (Thr196) of SIK3 in vivo (PMID:25996931, the source of the separate IMP row). Together these support Ser/Thr protein kinase activity for the fly protein. Supporting Evidence: PMID:25996931 Wild-type and kinase-dead (K70M) SIK3 were highly phosphorylated at Thr196 by LKB1 file:genes/DROME/Lkb1/Lkb1-uniprot.txt DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. file:genes/DROME/Lkb1/Lkb1-uniprot.txt DR Pfam; PF00069; Pkinase; 1. |
| GO:0005938 cell cortex | IDA PMID:18054329 The GC kinase Fray and Mo25 regulate Drosophila asymmetric d... | KEEP AS NON CORE | Summary: LKB1 accumulates at the cell cortex. Reason: LKB1 overexpression leads to cortical accumulation. Supporting Evidence: PMID:18054329 Lkb1, which accumulates in the cell cortex |
| GO:0072697 protein localization to cell cortex | IMP PMID:18054329 The GC kinase Fray and Mo25 regulate Drosophila asymmetric d... | KEEP AS NON CORE | Summary: LKB1 localizes to the cell cortex. Reason: LKB1 accumulates at the cell cortex in neuroblasts. Supporting Evidence: PMID:18054329 Lkb1, which accumulates in the cell cortex |
| GO:0072697 protein localization to cell cortex | IGI PMID:18054329 The GC kinase Fray and Mo25 regulate Drosophila asymmetric d... | KEEP AS NON CORE | Summary: LKB1 localizes to the cell cortex. Reason: LKB1 accumulates at the cell cortex in neuroblasts. Supporting Evidence: PMID:18054329 Lkb1, which accumulates in the cell cortex |
| GO:0045201 maintenance of neuroblast polarity | IDA PMID:22248825 Sgt1 acts via an LKB1/AMPK pathway to establish cortical pol... | KEEP AS NON CORE | Summary: LKB1 supports neuroblast cortical polarity. Reason: LKB1 mutants show apical cortical polarity defects in neuroblasts. Supporting Evidence: PMID:22248825 LKB1, or AMPKΞ± all show similar prophase apical cortical polarity defects |
| GO:0008340 determination of adult lifespan | IDA PMID:21281604 A gain-of-function screen identifies wdb and lkb1 as lifespa... | KEEP AS NON CORE | Summary: LKB1 overexpression extends lifespan in Drosophila. Reason: Gain-of-function lkb1 overexpression extends lifespan. Supporting Evidence: PMID:21281604 overexpression of the lkb1 gene encoding a serine/threonine kinase, reduced organ size and extended lifespan |
| GO:0007391 dorsal closure | IMP PMID:16273080 JNK pathway mediates apoptotic cell death induced by tumor s... | UNDECIDED | Summary: Dorsal closure is not explicitly supported by the available abstract evidence. Reason: The cited study discusses epithelial morphogenesis broadly, but not dorsal closure specifically. Supporting Evidence: PMID:16273080 Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:16273080 JNK pathway mediates apoptotic cell death induced by tumor s... | KEEP AS NON CORE | Summary: LKB1 promotes apoptosis via JNK signaling. Reason: LKB1 induces caspase-dependent apoptosis in Drosophila. Supporting Evidence: PMID:16273080 Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis |
| GO:0046328 regulation of JNK cascade | IDA PMID:16273080 JNK pathway mediates apoptotic cell death induced by tumor s... | KEEP AS NON CORE | Summary: LKB1 activates the JNK signaling pathway. Reason: The JNK pathway is activated by LKB1 and mediates LKB1-dependent apoptosis. Supporting Evidence: PMID:16273080 the JNK pathway was activated by LKB1 and mediated the LKB1-dependent apoptosis |
| GO:0030709 border follicle cell delamination | IMP PMID:18976916 PAR-1 kinase regulates epithelial detachment and directional... | UNDECIDED | Summary: Border follicle cell delamination is not supported for LKB1 in the cited abstract. Reason: The referenced study centers on PAR-1, not LKB1; direct evidence for LKB1 in border cell delamination is not accessible. Supporting Evidence: PMID:18976916 PAR-1 directly modulates apical-basal polarity between border cells and epithelial cells to promote detachment |
| GO:0005634 nucleus | IDA PMID:17507418 The Drosophila Lkb1 kinase is required for spindle formation... | KEEP AS NON CORE | Summary: LKB1 can localize to the nucleus per UniProt annotation. Reason: UniProt lists nucleus as a subcellular location. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}. Nucleus PMID:17507418 The Drosophila Lkb1 kinase is required for spindle formation and asymmetric neuroblast division. |
| GO:0005737 cytoplasm | IDA PMID:17507418 The Drosophila Lkb1 kinase is required for spindle formation... | KEEP AS NON CORE | Summary: LKB1 localizes to the cytoplasm. Reason: UniProt lists cytoplasmic localization. Supporting Evidence: file:genes/DROME/Lkb1/Lkb1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}. PMID:17507418 The Drosophila Lkb1 kinase is required for spindle formation and asymmetric neuroblast division. |
| GO:0007052 mitotic spindle organization | IMP PMID:17507418 The Drosophila Lkb1 kinase is required for spindle formation... | KEEP AS NON CORE | Summary: LKB1 is required for spindle formation. Reason: Mutations disrupt spindle formation in larval brains. Supporting Evidence: PMID:17507418 mutations disrupt spindle formation, resulting in frequent polyploid cells in larval brains |
| GO:0055059 asymmetric neuroblast division | IMP PMID:17507418 The Drosophila Lkb1 kinase is required for spindle formation... | KEEP AS NON CORE | Summary: LKB1 is required for asymmetric neuroblast division. Reason: Mutations affect asymmetric division of larval neuroblasts. Supporting Evidence: PMID:17507418 dlkb1 mutations affect asymmetric division of larval neuroblasts |
| GO:0016325 oocyte microtubule cytoskeleton organization | IMP PMID:12540903 A role for Drosophila LKB1 in anterior-posterior axis format... | KEEP AS NON CORE | Summary: LKB1 controls repolarization of the oocyte cytoskeleton. Reason: Lkb1 is required for repolarization of the oocyte cytoskeleton. Supporting Evidence: PMID:12540903 homologue, lkb1, is required for the early A-P polarity of the oocyte |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Lkb1 kinase (Lkb1) encodes a serine/threonine kinase that plays a master role for activating the AMP-dependent protein kinase (AMPK) family kinases. It is a well-characterized tumor suppressor and regulates processes like cell polarity, metabolism, apoptosis, and cell growth.
Loading supporting contentβ¦
Download this section (compressed HTML)