ALK is a single-pass cell-surface receptor tyrosine kinase whose extracellular domain binds ALKAL cytokines and heparin. Ligand-dependent receptor assembly promotes ATP-dependent tyrosine autophosphorylation and recruitment of intracellular signaling proteins, connecting extracellular signals to MAPK, PI3K and other context-dependent pathways. Human receptor structures and cellular assays establish ALKAL2-driven activation and condition-dependent activation by ALKAL1. Developmental and neuronal roles are supported by vertebrate models; mouse hypothalamic ALK also regulates energy expenditure and adipose lipid mobilization. Activating mutations and fusions deregulate the kinase in neuroblastoma and other cancers, but fusion proteins can differ substantially from the normal receptor in localization and ligand dependence.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine kinase chemistry to the established receptor tyrosine kinase activity. Reason: The annotation captures real kinase chemistry, but the established normal human protein is a transmembrane receptor tyrosine kinase, providing a more informative molecular-function term. Proposed replacements: transmembrane receptor protein tyrosine kinase activity Supporting Evidence: PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:30061385 Identification of a biologically active fragment of ALK and ... | MODIFY | Summary: Refine kinase chemistry to the established receptor tyrosine kinase activity. Reason: The annotation captures real kinase chemistry, but the established normal human protein is a transmembrane receptor tyrosine kinase, providing a more informative molecular-function term. Proposed replacements: transmembrane receptor protein tyrosine kinase activity Supporting Evidence: PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. |
| GO:0004713 protein tyrosine kinase activity | EXP PMID:34819673 Mechanism for the activation of the anaplastic lymphoma kina... | MODIFY | Summary: Refine kinase chemistry to the established receptor tyrosine kinase activity. Reason: The annotation captures real kinase chemistry, but the established normal human protein is a transmembrane receptor tyrosine kinase, providing a more informative molecular-function term. Proposed replacements: transmembrane receptor protein tyrosine kinase activity Supporting Evidence: PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. |
| GO:0004713 protein tyrosine kinase activity | IDA PMID:9174053 ALK, the chromosome 2 gene locus altered by the t(2;5) in no... | MODIFY | Summary: Refine kinase chemistry to the established receptor tyrosine kinase activity. Reason: The annotation captures real kinase chemistry, but the established normal human protein is a transmembrane receptor tyrosine kinase, providing a more informative molecular-function term. The original cache is abstract-only; this refinement uses its full-length human receptor identification together with independent human ligand/structural studies, without claiming that the unavailable original Results were read. Proposed replacements: transmembrane receptor protein tyrosine kinase activity Supporting Evidence: PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: Refine kinase chemistry to the established receptor tyrosine kinase activity. Reason: The annotation captures real kinase chemistry, but the established normal human protein is a transmembrane receptor tyrosine kinase, providing a more informative molecular-function term. The InterPro/RHEA mapping is compatible with this chemistry; it is a specificity refinement, not evidence of an erroneous catalytic assignment. Proposed replacements: transmembrane receptor protein tyrosine kinase activity Supporting Evidence: PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-201521 | MODIFY | Summary: Refine kinase chemistry to the established receptor tyrosine kinase activity. Reason: The annotation captures real kinase chemistry, but the established normal human protein is a transmembrane receptor tyrosine kinase, providing a more informative molecular-function term. The model describes tyrosine trans-autophosphorylation of the receptor and notes that some additional ALK phosphosites may be modified by other kinases. Its historical ALK1 wording denotes ALK here, not ACVRL1. Proposed replacements: transmembrane receptor protein tyrosine kinase activity Supporting Evidence: PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-9700168 | ACCEPT | Summary: Retain the tyrosine kinase activity at the resolution of this reaction model. Reason: IRS1 phosphorylation is modeled from kinase-dependent fusion-protein evidence; the summary leaves exact full-length ALK target sites unresolved. ALK tyrosine kinase chemistry is independently established. Retaining this molecular activity does not certify every proposed immediate substrate or assign transmembrane topology to truncated fusion constructs. Supporting Evidence: PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-9700171 | ACCEPT | Summary: Retain the tyrosine kinase activity at the resolution of this reaction model. Reason: PLCG1 phosphorylation is extrapolated from NPM–ALK experiments; binding-site mutants and cell transformation are not purified direct-substrate measurements. ALK tyrosine kinase chemistry is independently established. Retaining this molecular activity does not certify every proposed immediate substrate or assign transmembrane topology to truncated fusion constructs. Supporting Evidence: PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-9700175 | ACCEPT | Summary: Retain the tyrosine kinase activity at the resolution of this reaction model. Reason: SHC1 phosphorylation is kinase dependent, but the model distinguishes experimentally supported dependence from presumed individual target sites. ALK tyrosine kinase chemistry is independently established. Retaining this molecular activity does not certify every proposed immediate substrate or assign transmembrane topology to truncated fusion constructs. Supporting Evidence: PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-9700193 | ACCEPT | Summary: Retain the tyrosine kinase activity at the resolution of this reaction model. Reason: SHC phosphorylation downstream of mutant ALK varies with the fusion context; the broad catalytic term does not claim a normal transmembrane topology for every fusion. ALK tyrosine kinase chemistry is independently established. Retaining this molecular activity does not certify every proposed immediate substrate or assign transmembrane topology to truncated fusion constructs. Supporting Evidence: PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-9701488 | ACCEPT | Summary: Retain the tyrosine kinase activity at the resolution of this reaction model. Reason: The summary reports JAK3 phosphorylation downstream of active ALK in cellular/fusion contexts; it does not establish purified direct ALK-to-JAK3 phosphotransfer. ALK tyrosine kinase chemistry is independently established. Retaining this molecular activity does not certify every proposed immediate substrate or assign transmembrane topology to truncated fusion constructs. Supporting Evidence: PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-NUL-9700161 | ACCEPT | Summary: Retain the tyrosine kinase activity at the resolution of this reaction model. Reason: The R-NUL summary concerns kinase-dependent Frs2 phosphorylation in heterologous human-ALK experiments. A cross-species substrate assay is not a direct human-tissue pathway measurement. ALK tyrosine kinase chemistry is independently established. Retaining this molecular activity does not certify every proposed immediate substrate or assign transmembrane topology to truncated fusion constructs. Supporting Evidence: PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-NUL-9700655 | ACCEPT | Summary: Retain the tyrosine kinase activity at the resolution of this reaction model. Reason: The R-NUL summary describes endogenous Src phosphorylation in Ba/F3 cells expressing human NPM–ALK; fusion kinase evidence is not normal receptor-topology evidence. ALK tyrosine kinase chemistry is independently established. Retaining this molecular activity does not certify every proposed immediate substrate or assign transmembrane topology to truncated fusion constructs. Supporting Evidence: PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. |
| GO:0004714 transmembrane receptor protein tyrosine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: ALK is a transmembrane receptor tyrosine kinase. Reason: Normal human ALK binds extracellular cytokines and couples receptor assembly to intracellular tyrosine phosphorylation. Human full-length receptor assays, extracellular structures and kinase studies support this defining activity. The actual PAINT IBD at PTN001230349 was inspected; this is inherited receptor-kinase function, not a pairwise donor-count argument. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001230349 SUPPORTS TRANSFER Matching IBD inspected in PTHR24416-paint.tsv; direct target-human receptor evidence corroborates the inherited activity/location/complex. Descendant donor count and target self-inclusion do not weaken the assertion. Supporting Evidence: PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK |
| GO:0004714 transmembrane receptor protein tyrosine kinase activity | IDA PMID:30061385 Identification of a biologically active fragment of ALK and ... | ACCEPT | Summary: ALK is a transmembrane receptor tyrosine kinase. Reason: Normal human ALK binds extracellular cytokines and couples receptor assembly to intracellular tyrosine phosphorylation. Human full-length receptor assays, extracellular structures and kinase studies support this defining activity. Supporting Evidence: PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK |
| GO:0004714 transmembrane receptor protein tyrosine kinase activity | IDA PMID:34646012 Structural basis of cytokine-mediated activation of ALK fami... | ACCEPT | Summary: ALK is a transmembrane receptor tyrosine kinase. Reason: Normal human ALK binds extracellular cytokines and couples receptor assembly to intracellular tyrosine phosphorylation. Human full-length receptor assays, extracellular structures and kinase studies support this defining activity. Supporting Evidence: PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK |
| GO:0004714 transmembrane receptor protein tyrosine kinase activity | IDA PMID:9174053 ALK, the chromosome 2 gene locus altered by the t(2;5) in no... | ACCEPT | Summary: ALK is a transmembrane receptor tyrosine kinase. Reason: Normal human ALK binds extracellular cytokines and couples receptor assembly to intracellular tyrosine phosphorylation. Human full-length receptor assays, extracellular structures and kinase studies support this defining activity. The 1997 abstract identifies the full-length normal human receptor; its murine expression map is not a human developmental assay. The linked 1997 erratum body remains unrecovered; independent later human studies corroborate the activity. Supporting Evidence: PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK |
| GO:0004714 transmembrane receptor protein tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: ALK is a transmembrane receptor tyrosine kinase. Reason: Normal human ALK binds extracellular cytokines and couples receptor assembly to intracellular tyrosine phosphorylation. Human full-length receptor assays, extracellular structures and kinase studies support this defining activity. IPR002011 and EC:2.7.10.1 describe the appropriate receptor class. Supporting Evidence: PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK |
| GO:0004714 transmembrane receptor protein tyrosine kinase activity | TAS PMID:19459784 Anaplastic lymphoma kinase: signalling in development and di... | ACCEPT | Summary: ALK is a transmembrane receptor tyrosine kinase. Reason: Normal human ALK binds extracellular cytokines and couples receptor assembly to intracellular tyrosine phosphorylation. Human full-length receptor assays, extracellular structures and kinase studies support this defining activity. The review is secondary evidence and predates ALKAL identification; later primary studies resolve the ligand framework. Supporting Evidence: PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK |
| GO:0005515 protein binding | IPI PMID:17681947 Anaplastic lymphoma kinase is activated through the pleiotro... | UNDECIDED | Summary: Retain uncertainty about the precise ALK–PTPRZ interaction assay. Reason: The accessible abstract reports PTPRZ-mediated ALK dephosphorylation and an indirect PTN route. It does not expose the pair-level binding assay used for this IPI assertion. The claim is not rejected because the paper is about a phosphatase or because PTN does not directly bind ALK; no mechanistic binding replacement is manufactured from an unread assay. Supporting Evidence: PMID:17681947 ALK is phosphorylated independently of a direct interaction of PTN with ALK. |
| GO:0005515 protein binding | IPI PMID:22939624 Quantitative analysis of HSP90-client interactions reveals p... | UNDECIDED | Summary: The HSP90-client interaction requires its ALK-specific evidence. Reason: The recovered HSP90 study contains partial HTML full-text extraction, but the exact ALK–HSP90AB1 client measurement was not recovered from its supporting data. The general client survey does not establish that this pair is false, and it does not support a more specific ALK molecular function. |
| GO:0005515 protein binding | IPI PMID:26418745 FAM150A and FAM150B are activating ligands for anaplastic ly... | MODIFY | Summary: Represent ALKAL ligand recognition as cytokine binding. Reason: The source directly measures binding of human ALK to FAM150A/B (ALKAL1/2). Purified human FAM150A binds the human ALK extracellular domain by ELISA and surface plasmon resonance, and both ligands associate in reciprocal immunoprecipitations. The independent human receptor structures in PMID:34646012 identify their cytokine-binding interface. GO:0019955 therefore preserves the measured ligand-binding function and the named IPI partner; replacing it with kinase catalysis would lose that information and duplicate an already retained function. This does not assert equal physiological potency of the two cytokines. Proposed replacements: cytokine binding Supporting Evidence: PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK PMID:26418745 Both ELISA and Biacore analysis showed that FAM150A binds specifically to the ALK ECD |
| GO:0005515 protein binding | IPI PMID:26418745 FAM150A and FAM150B are activating ligands for anaplastic ly... | MODIFY | Summary: Represent ALKAL ligand recognition as cytokine binding. Reason: The source directly measures binding of human ALK to FAM150A/B (ALKAL1/2). Purified human FAM150A binds the human ALK extracellular domain by ELISA and surface plasmon resonance, and both ligands associate in reciprocal immunoprecipitations. The independent human receptor structures in PMID:34646012 identify their cytokine-binding interface. GO:0019955 therefore preserves the measured ligand-binding function and the named IPI partner; replacing it with kinase catalysis would lose that information and duplicate an already retained function. This does not assert equal physiological potency of the two cytokines. Proposed replacements: cytokine binding Supporting Evidence: PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK PMID:26418745 Both ELISA and Biacore analysis showed that FAM150A binds specifically to the ALK ECD |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | UNDECIDED | Summary: The ALK–SHC1 screen-level interaction remains source-limited. Reason: BioPlex is a genuine human interaction dataset, but the precise ALK–SHC1 supporting-data row and construct context were not recovered in the cached extraction. Independent receptor signaling makes the interaction plausible, but is not a substitute for this source-specific IPI assay. |
| GO:0005515 protein binding | IPI PMID:34606829 Mapping the Phospho-dependent ALK Interactome to Identify No... | KEEP AS NON CORE | Summary: NCK2 is an experimentally supported ALK interactor. Reason: The abstract explicitly reports co-immunoprecipitation verification of NCK2 in neuroblastoma cells. This preserves the positive interaction at its observed resolution. Generic protein binding adds little to the integrated receptor mechanism and does not by itself establish a specific adaptor or direct substrate function for ALK. Supporting Evidence: PMID:34606829 Among the novel interactors, NCK2 was further verified in neuroblastoma cells using co-immunoprecipitation. |
| GO:0005515 protein binding | IPI PMID:34606829 Mapping the Phospho-dependent ALK Interactome to Identify No... | UNDECIDED | Summary: The PIK3R1 interaction requires the source-specific screen result. Reason: The accessible abstract describes MaMTH profiling of SH2 proteins and names NCK2 validation, but the exact PIK3R1 pair-level evidence and validation were not recovered. This is an access limitation, not evidence against the reported interaction or a license to infer direct phosphorylation. Supporting Evidence: PMID:34606829 Among the novel interactors, NCK2 was further verified in neuroblastoma cells using co-immunoprecipitation. |
| GO:0005515 protein binding | IPI PMID:34606829 Mapping the Phospho-dependent ALK Interactome to Identify No... | UNDECIDED | Summary: The SHC1 interaction requires the source-specific screen result. Reason: The accessible abstract describes MaMTH profiling of SH2 proteins and names NCK2 validation, but the exact SHC1 pair-level evidence and validation were not recovered. This is an access limitation, not evidence against the reported interaction or a license to infer direct phosphorylation. Supporting Evidence: PMID:34606829 Among the novel interactors, NCK2 was further verified in neuroblastoma cells using co-immunoprecipitation. |
| GO:0005515 protein binding | IPI PMID:35384245 Physical and functional interactome atlas of human receptor ... | UNDECIDED | Summary: The atlas interaction with RET remains source-limited. Reason: The full receptor-kinase atlas contains human ALK constructs and proximity/affinity interaction assays, but the exact ALK–RET supporting-data experiment was not recovered. Network membership alone does not determine a specific biochemical function. The positive source assertion is not declared false. |
| GO:0005515 protein binding | IPI PMID:35384245 Physical and functional interactome atlas of human receptor ... | UNDECIDED | Summary: The atlas interaction with PIK3R1 remains source-limited. Reason: The full receptor-kinase atlas contains human ALK constructs and proximity/affinity interaction assays, but the exact ALK–PIK3R1 supporting-data experiment was not recovered. Network membership alone does not determine a specific biochemical function. The positive source assertion is not declared false. |
| GO:0005515 protein binding | IPI PMID:35384245 Physical and functional interactome atlas of human receptor ... | UNDECIDED | Summary: The atlas interaction with SHC1 remains source-limited. Reason: The full receptor-kinase atlas contains human ALK constructs and proximity/affinity interaction assays, but the exact ALK–SHC1 supporting-data experiment was not recovered. Network membership alone does not determine a specific biochemical function. The positive source assertion is not declared false. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding is integral to ALK kinase catalysis. Reason: The kinase-domain mappings are corroborated by purified human ALK kinase measurements of ATP-dependent activity in PMID:25517749. This is a genuine catalytic substrate interaction and is represented within the integrated receptor-kinase core rather than as an unrelated binding function. Supporting Evidence: PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the normal receptor plasma-membrane location. Reason: Full-length normal human ALK is a single-pass cell-surface receptor; the original human surface-labeling result and modern receptor assays support plasma-membrane localization. PTN001230349 has a matching PAINT IBD. Human ALK appearing among the descendant evidence is expected experimental grounding, not circularity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001230349 SUPPORTS TRANSFER Matching IBD inspected in PTHR24416-paint.tsv; direct target-human receptor evidence corroborates the inherited activity/location/complex. Descendant donor count and target self-inclusion do not weaken the assertion. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Retain the normal receptor plasma-membrane location. Reason: Full-length normal human ALK is a single-pass cell-surface receptor; the original human surface-labeling result and modern receptor assays support plasma-membrane localization. The current Human Protein Atlas reports supported plasma-membrane staining with HPA010694 in Rh30 cells; SH-SY5Y has no staining in the displayed experiment, so this is not generalized to every cell line. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | IDA PMID:34646012 Structural basis of cytokine-mediated activation of ALK fami... | ACCEPT | Summary: Retain the normal receptor plasma-membrane location. Reason: Full-length normal human ALK is a single-pass cell-surface receptor; the original human surface-labeling result and modern receptor assays support plasma-membrane localization. The source combines human receptor extracellular structures with cellular activation assays, not a claim that purified fragments themselves span a membrane. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | IDA PMID:9174053 ALK, the chromosome 2 gene locus altered by the t(2;5) in no... | ACCEPT | Summary: Retain the normal receptor plasma-membrane location. Reason: Full-length normal human ALK is a single-pass cell-surface receptor; the original human surface-labeling result and modern receptor assays support plasma-membrane localization. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Retain the normal receptor plasma-membrane location. Reason: Full-length normal human ALK is a single-pass cell-surface receptor; the original human surface-labeling result and modern receptor assays support plasma-membrane localization. UniProt SL-0039 supplies a consistent curated location mapping. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS PMID:19459784 Anaplastic lymphoma kinase: signalling in development and di... | ACCEPT | Summary: Retain the normal receptor plasma-membrane location. Reason: Full-length normal human ALK is a single-pass cell-surface receptor; the original human surface-labeling result and modern receptor assays support plasma-membrane localization. The secondary review distinguishes normal full-length ALK from oncogenic fusions; fusion localization is not automatically transferred to the normal receptor. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201486 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: This legacy model describes direct PTN binding. PMID:17681947 instead demonstrates an indirect PTN–PTPRZ route, and the ALKAL studies establish direct cytokine ligands. The model title does not settle direct PTN binding. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201510 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: PI3K performs PIP3 synthesis downstream of ALK; this does not assign lipid kinase chemistry to ALK. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201515 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: The recruitment model relies substantially on NPM–ALK and allows an unidentified adaptor; it explicitly limits evidence for PI3K activation downstream of ALKAL ligands. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201521 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: The model describes tyrosine trans-autophosphorylation of the receptor and notes that some additional ALK phosphosites may be modified by other kinases. Its historical ALK1 wording denotes ALK here, not ACVRL1. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9667914 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: Direct MDK binding is a historical model whose physiological ligand interpretation is less secure than the ALKAL evidence; the localization assertion does not establish the ligand mechanism. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700114 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: This is an inhibitor-resistance model for selected ALK mutants, not a new normal-receptor localization experiment. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700131 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: This model describes type-I inhibitor binding to selected ALK mutants and fusions; those constructs need not retain the topology of normal ALK. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700149 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: PLCG1 recruitment is modeled partly from NPM–ALK and its Y1604-equivalent site; normal receptor and oncogenic-fusion evidence are distinguished. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700154 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: The model describes SHC1 recruitment to full-length phosphorylated ALK, with Y1507 and kinase dependence considered separately from downstream differentiation. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700156 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: The model concerns IRS1 docking at the intracellular ALK phosphotyrosine region, rather than an independent membrane-imaging assay. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700168 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: IRS1 phosphorylation is modeled from kinase-dependent fusion-protein evidence; the summary leaves exact full-length ALK target sites unresolved. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700171 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: PLCG1 phosphorylation is extrapolated from NPM–ALK experiments; binding-site mutants and cell transformation are not purified direct-substrate measurements. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700175 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: SHC1 phosphorylation is kinase dependent, but the model distinguishes experimentally supported dependence from presumed individual target sites. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700184 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: This model concerns selected activating point mutants and ligand-independent receptor assembly; it does not imply that every ALK variant is constitutively active. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700186 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: Activating point-mutant autophosphorylation supports the conserved tyrosine kinase chemistry, with mutation-specific activation distinguished from normal ligand control. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700190 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: The summary includes NPM–ALK/SHC co-immunoprecipitation in NIH3T3 cells and notes that SHC binding is not essential for transformation in that model. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700193 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: SHC phosphorylation downstream of mutant ALK varies with the fusion context; the broad catalytic term does not claim a normal transmembrane topology for every fusion. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700200 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: The model explicitly discusses competing direct-ligand and indirect PTN–PTPRZ mechanisms. PTPRZ performs dephosphorylation; ALK remains the regulated receptor kinase. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700646 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: This is selected-mutant resistance to ASP-3026, with no independent normal-receptor localization assay. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700656 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: This is selected-mutant resistance to alectinib, with no inference that all ALK-containing fusions are membrane receptors. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700658 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: This is selected-mutant resistance to ceritinib, rather than a new physiological activity. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700662 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: The model describes inhibitor binding to liganded ALK receptor dimers; inhibitor response is distinct from receptor location. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9701485 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: JAK3 association is based substantially on NPM–ALK coexpression, and downstream STAT3/JAK3 dependence is context dependent. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9701488 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: The summary reports JAK3 phosphorylation downstream of active ALK in cellular/fusion contexts; it does not establish purified direct ALK-to-JAK3 phosphotransfer. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9701507 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: PTPN6 is the phosphatase acting on JAK3 in this model; the source must not be read as ALK phosphatase activity. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9701524 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: STAT3 phosphorylation is downstream of ALK, with direct versus JAK3-mediated tyrosine phosphorylation unsettled and serine phosphorylation attributed to other pathways. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9712078 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: PIK3R1 association with mutant ALK can be mediated by adaptors; the model does not by itself establish an intrinsic ALK adaptor activity. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9712079 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: STAT3 association is a mutant/fusion signaling context, with the immediate phosphorylating enzyme not uniformly established. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9712083 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: This model represents PI3K recruitment downstream of mutant ALK, not ALK lipid-kinase catalysis. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9712084 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: PI3K, rather than ALK, performs the modeled PIP3 synthesis downstream of ALK mutants. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9712085 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: This model represents STAT3 tyrosine phosphorylation downstream of mutant ALK; it does not assign DNA binding or transcription-factor activity to ALK. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9715355 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: This source models selected-mutant resistance to lorlatinib rather than physiological receptor localization. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9715356 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: This source models selected-mutant resistance to brigatinib rather than a new normal ALK function. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9715357 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: This source models selected-mutant resistance to crizotinib; fusion-specific behavior is not generalized to normal ALK. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9724099 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: The model includes SHC/GRB2 signaling complexes downstream of ALK mutants; direct versus adaptor-mediated association depends on the construct. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9725117 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: This source models regulation of ALK gene expression, including MYCN-associated neuroblastoma context. ALK is the expressed product, not the transcriptional machinery. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9842656 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: Direct ALKAL binding is supported by human receptor studies. ALKAL2 potency, weaker or condition-dependent ALKAL1 activation, heparin modulation and construct-dependent stoichiometry are distinguished. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9850958 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: STAT3, not necessarily ALK itself, translocates to the nucleus in this downstream signaling event. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-NUL-9700145 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: The R-NUL summary concerns rat Frs2 and human ALK in heterologous cells; mixed species and the literal HEK203 wording are retained as source limitations. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-NUL-9700161 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: The R-NUL summary concerns kinase-dependent Frs2 phosphorylation in heterologous human-ALK experiments. A cross-species substrate assay is not a direct human-tissue pathway measurement. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-NUL-9700655 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: The R-NUL summary describes endogenous Src phosphorylation in Ba/F3 cells expressing human NPM–ALK; fusion kinase evidence is not normal receptor-topology evidence. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-NUL-9700661 | ACCEPT | Summary: Retain the normal ALK plasma-membrane assertion at pathway-model resolution. Reason: The R-NUL summary describes Src association with human NPM–ALK in Ba/F3 cells; association and native membrane residence are separate claims. The seeded term is a location assertion. Its acceptance uses the curated normal-receptor placement and independent human surface labeling; it does not turn the event title into an additional ALK activity or a direct localization assay, and does not imply that all oncogenic fusions share this location. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0007165 signal transduction | TAS PMID:19459784 Anaplastic lymphoma kinase: signalling in development and di... | MODIFY | Summary: Refine broad signaling to the receptor tyrosine kinase pathway. Reason: ALK itself performs receptor kinase signaling, rather than merely being a regulated downstream substrate. The source review and later ligand experiments identify a more precise process than generic signal transduction. Proposed replacements: cell surface receptor protein tyrosine kinase signaling pathway Supporting Evidence: PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK |
| GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: ALK directly performs receptor tyrosine kinase signaling. Reason: Ligand binding, receptor assembly and receptor tyrosine phosphorylation establish the signaling step performed by ALK. Downstream MAPK or PI3K outputs are contextual consequences, not evidence that ALK performs every downstream catalytic reaction. The matching PTN001230349 IBD was inspected; target-specific human evidence supports its inherited placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001230349 SUPPORTS TRANSFER Matching IBD inspected in PTHR24416-paint.tsv; direct target-human receptor evidence corroborates the inherited activity/location/complex. Descendant donor count and target self-inclusion do not weaken the assertion. Supporting Evidence: PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. |
| GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway | IDA PMID:30061385 Identification of a biologically active fragment of ALK and ... | ACCEPT | Summary: ALK directly performs receptor tyrosine kinase signaling. Reason: Ligand binding, receptor assembly and receptor tyrosine phosphorylation establish the signaling step performed by ALK. Downstream MAPK or PI3K outputs are contextual consequences, not evidence that ALK performs every downstream catalytic reaction. Supporting Evidence: PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. |
| GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway | IDA PMID:34646012 Structural basis of cytokine-mediated activation of ALK fami... | ACCEPT | Summary: ALK directly performs receptor tyrosine kinase signaling. Reason: Ligand binding, receptor assembly and receptor tyrosine phosphorylation establish the signaling step performed by ALK. Downstream MAPK or PI3K outputs are contextual consequences, not evidence that ALK performs every downstream catalytic reaction. Supporting Evidence: PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. |
| GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: ALK directly performs receptor tyrosine kinase signaling. Reason: Ligand binding, receptor assembly and receptor tyrosine phosphorylation establish the signaling step performed by ALK. Downstream MAPK or PI3K outputs are contextual consequences, not evidence that ALK performs every downstream catalytic reaction. Supporting Evidence: PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. |
| GO:0007399 nervous system development | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain the conserved developmental role with donor and model limits. Reason: The combined inference includes rat-source identifiers and ARBA. The MGI comparative graph traces rat developmental evidence to PMID:11121404, whose accessible abstract reports Fc-chimeric ALK in PC12 cells; the receptor construct species cannot be inferred from the rat host alone. Independent human receptor activation can induce neuronal differentiation in cellular models, and mouse/zebrafish studies support developmental roles. This supports a contextual vertebrate developmental annotation without inventing a direct normal-human developmental experiment. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:F1LRZ0 UNRESOLVED Rat-source graph resolves to PMID:11121404, but the accessible chimera abstract does not establish receptor construct species; host species is not used as a substitute. ARBA:ARBA00027428 UNRESOLVED Combined rule provenance is retained; the complete rule inference was not independently reconstructed. Supporting Evidence: PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK |
| GO:0008201 heparin binding | IDA PMID:25605972 Heparin is an activating ligand of the orphan receptor tyros... | ACCEPT | Summary: ALK directly binds heparin through its extracellular region. Reason: The original abstract distinguishes short-chain binding without activation from longer-chain heparin-induced receptor dimerization and activation. This supports binding directly; it does not make all glycosaminoglycans equivalent ligands or displace the ALKAL cytokine mechanism. Supporting Evidence: PMID:25605972 We found that heparin is a ligand that binds specifically to the ALK extracellular domain. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Membrane association is a correct broad location for ALK. Reason: The InterPro domain architecture and independent human surface labeling support membrane residence. This source-level location remains true at its broad resolution; the more precise plasma-membrane rows already capture the established compartment. Supporting Evidence: PMID:9174053 Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane |
| GO:0016310 phosphorylation | IDA PMID:9174053 ALK, the chromosome 2 gene locus altered by the t(2;5) in no... | MODIFY | Summary: Refine phosphorylation to tyrosine autophosphorylation. Reason: The source annotation is broad. Human receptor kinase studies and the curated activation-loop mechanism identify peptidyl-tyrosine autophosphorylation specifically. The original abstract alone does not expose its phosphorylation assay, so the refinement explicitly uses independent evidence rather than asserting unseen 1997 Results. Proposed replacements: peptidyl-tyrosine autophosphorylation Supporting Evidence: PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. Reactome:R-HSA-201521 Trans-phosphorylation of the three tyrosine residues in the activation (Y1278, Y1282 and Y1283) after ligand binding causes a conformational change that relieves autoinhibition of the kinase |
| GO:0030298 receptor signaling protein tyrosine kinase activator activity | IDA PMID:30061385 Identification of a biologically active fragment of ALK and ... | UNDECIDED | Summary: Separate noncovalent kinase activation from ALK autophosphorylation. Reason: The 2018 study directly assays the activating ligand fragment; receptor–receptor activation is discussed rather than separately isolated. GO:0030298 has molecular-function-regulator ancestry explicitly restricting the activity to noncovalent modulation. The positive assembly/phosphorylation evidence does not yet distinguish an ALK-mediated noncovalent increase in another kinase domain from trans-autophosphorylation. Retain uncertainty rather than rejecting a genuine receptor–receptor interaction or asserting a separate activator core. The unresolved issue is whether receptor association itself allosterically increases partner catalytic activity when receptor phosphotransfer is experimentally separated from that association, rather than merely positioning two kinase domains for trans-phosphorylation. An interface-controlled reconstitution with fixed receptor phosphorylation state and independently measured partner substrate turnover would resolve this. The uncertainty concerns mechanism despite access to the full sources, not missing text; the term definition does not forbid a receptor from acting on another receptor. Supporting Evidence: PMID:34646012 Sites 1 and 2 correspond to receptor–cytokine interactions and site 3 describes receptor–receptor contacts PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. |
| GO:0030298 receptor signaling protein tyrosine kinase activator activity | IDA PMID:34646012 Structural basis of cytokine-mediated activation of ALK fami... | UNDECIDED | Summary: Separate noncovalent kinase activation from ALK autophosphorylation. Reason: The 2021 source directly establishes ALK receptor–receptor contacts and tests the M751T interface variant in Ba/F3 cells, so the receptor is not dismissed as an impossible activator. GO:0030298 has molecular-function-regulator ancestry explicitly restricting the activity to noncovalent modulation. The positive assembly/phosphorylation evidence does not yet distinguish an ALK-mediated noncovalent increase in another kinase domain from trans-autophosphorylation. Retain uncertainty rather than rejecting a genuine receptor–receptor interaction or asserting a separate activator core. The unresolved issue is whether receptor association itself allosterically increases partner catalytic activity when receptor phosphotransfer is experimentally separated from that association, rather than merely positioning two kinase domains for trans-phosphorylation. An interface-controlled reconstitution with fixed receptor phosphorylation state and independently measured partner substrate turnover would resolve this. The uncertainty concerns mechanism despite access to the full sources, not missing text; the term definition does not forbid a receptor from acting on another receptor. Supporting Evidence: PMID:34646012 Sites 1 and 2 correspond to receptor–cytokine interactions and site 3 describes receptor–receptor contacts PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. |
| GO:0030298 receptor signaling protein tyrosine kinase activator activity | IEA GO_REF:0000117 | UNDECIDED | Summary: Separate noncovalent kinase activation from ALK autophosphorylation. Reason: The ARBA assignment repeats an activity whose distinction from receptor kinase activation remains unresolved; the exact training decision was not reconstructed. GO:0030298 has molecular-function-regulator ancestry explicitly restricting the activity to noncovalent modulation. The positive assembly/phosphorylation evidence does not yet distinguish an ALK-mediated noncovalent increase in another kinase domain from trans-autophosphorylation. Retain uncertainty rather than rejecting a genuine receptor–receptor interaction or asserting a separate activator core. The unresolved issue is whether receptor association itself allosterically increases partner catalytic activity when receptor phosphotransfer is experimentally separated from that association, rather than merely positioning two kinase domains for trans-phosphorylation. An interface-controlled reconstitution with fixed receptor phosphorylation state and independently measured partner substrate turnover would resolve this. The uncertainty concerns mechanism despite access to the full sources, not missing text; the term definition does not forbid a receptor from acting on another receptor. Propagation Review Root cause: UNRESOLVED Sources checked: ARBA:ARBA00034178 UNRESOLVED The rule-level provenance is known but the noncovalent-activation versus autophosphorylation distinction remains unresolved. Supporting Evidence: PMID:34646012 Sites 1 and 2 correspond to receptor–cytokine interactions and site 3 describes receptor–receptor contacts PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. |
| GO:0032991 protein-containing complex | IDA PMID:23382219 Structural basis for endosomal trafficking of diverse transm... | UNDECIDED | Summary: The original complex assertion requires its ALK-specific experiment. Reason: The recovered PX-FERM/endosomal-trafficking extraction does not expose the ALK-specific complex or supporting-data result. This does not establish a wrong-gene annotation: a paper focused on other cargos can assay ALK. Independently established ALK signaling-receptor assemblies do not identify the complex intended by this source. If the source-specific assembly proves to be the signaling-receptor complex, GO:0043235 would provide the informative refinement already supported elsewhere. That conditional destination does not establish the identity of the presently unresolved source complex. |
| GO:0038083 peptidyl-tyrosine autophosphorylation | IDA PMID:30061385 Identification of a biologically active fragment of ALK and ... | ACCEPT | Summary: ALK directly performs tyrosine autophosphorylation during activation. Reason: Human ALK ligand-response experiments and the receptor activation mechanism support tyrosine autophosphorylation. The term includes phosphorylation between identical receptor polypeptides; it does not require cis modification within one molecule. Supporting Evidence: PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. Reactome:R-HSA-201521 Trans-phosphorylation of the three tyrosine residues in the activation (Y1278, Y1282 and Y1283) after ligand binding causes a conformational change that relieves autoinhibition of the kinase |
| GO:0038083 peptidyl-tyrosine autophosphorylation | IDA PMID:34646012 Structural basis of cytokine-mediated activation of ALK fami... | ACCEPT | Summary: ALK directly performs tyrosine autophosphorylation during activation. Reason: Human ALK ligand-response experiments and the receptor activation mechanism support tyrosine autophosphorylation. The term includes phosphorylation between identical receptor polypeptides; it does not require cis modification within one molecule. Supporting Evidence: PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. Reactome:R-HSA-201521 Trans-phosphorylation of the three tyrosine residues in the activation (Y1278, Y1282 and Y1283) after ligand binding causes a conformational change that relieves autoinhibition of the kinase |
| GO:0042127 regulation of cell population proliferation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain a context-dependent role in controlling cell population proliferation. Reason: The actual PTN000699408 IBD is grounded in mouse Alk evidence. The MGI donor graph points to PMID:17487225, whose abstract reports increased basal hippocampal progenitor proliferation after kinase-domain deletion in adult mice. The unsigned regulation term fits this context without converting it to a universal growth-promoting effect. Human tumor-cell and ligand-response studies provide separate contexts, not a substitute for this donor assay. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000699408 SUPPORTS TRANSFER Matching IBD uses MGI:103305; term-specific mouse donor source is PMID:17487225. Adult hippocampal proliferation context is retained without asserting a universal sign. |
| GO:0042802 identical protein binding | IPI PMID:25517749 ALK mutations confer differential oncogenic activation and s... | ACCEPT | Summary: Receptor self-association is part of ALK activation. Reason: The precise self-interaction experiment in PMID:25517749 was not located in the recovered main text, which chiefly establishes kinase and mutant activity. Curator deference is supported by independent direct human ALK receptor–receptor structures and interface perturbation in PMID:34646012 and PMID:34819673. This accepts the biological assertion without pretending that the original pair-specific assay was recovered. Supporting Evidence: PMID:34646012 Sites 1 and 2 correspond to receptor–cytokine interactions and site 3 describes receptor–receptor contacts PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. |
| GO:0042981 regulation of apoptotic process | TAS PMID:19459784 Anaplastic lymphoma kinase: signalling in development and di... | KEEP AS NON CORE | Summary: ALK can regulate apoptosis in defined signaling and cell contexts. Reason: The review describes survival signaling from activated ALK and proposed dependence-receptor/caspase-cleavage behavior in cellular systems. These support the broad unsigned regulation term as contextual biology. They do not establish a uniform direction, physiological dependence-receptor mechanism in every tissue, or intrinsic ALK protease activity. Supporting Evidence: PMID:19459784 ALK displays the classical structural features of a RTK, with an extracellular ligand-binding domain, a transmembrane-spanning region and an intracellular tyrosine kinase domain. |
| GO:0043235 signaling receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: ALK is part of a ligand-responsive signaling receptor complex. Reason: The PTN001230349 inherited complex annotation is compatible with direct human ALK–cytokine and receptor–receptor structures. Different soluble constructs and ligand preparations yield differing stoichiometries; no single fixed native oligomeric composition is imposed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001230349 SUPPORTS TRANSFER Matching IBD inspected in PTHR24416-paint.tsv; direct target-human receptor evidence corroborates the inherited activity/location/complex. Descendant donor count and target self-inclusion do not weaken the assertion. Supporting Evidence: PMID:34646012 Sites 1 and 2 correspond to receptor–cytokine interactions and site 3 describes receptor–receptor contacts PMID:34819673 Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. |
| GO:0045664 regulation of neuron differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain regulation of neuronal differentiation as a developmental context. Reason: The PTN000699407 IBD explicitly traces to zebrafish Alk. PMID:23667670 reports embryonic knockdown/inhibitor and overexpression experiments affecting neuronal differentiation, survival and positioning, with progenitor and postmitotic effects distinguished. Human-receptor cell assays independently corroborate a differentiation-signaling capability; neither route is a direct intact-human nervous-system experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000699407 SUPPORTS TRANSFER Matching IBD uses ZFIN:ZDB-GENE-031027-1; PMID:23667670 supports the developmental source context. Human receptor differentiation assays corroborate transfer without recreating the whole phylogenetic analysis. |
| GO:0046777 protein autophosphorylation | IDA PMID:9174053 ALK, the chromosome 2 gene locus altered by the t(2;5) in no... | MODIFY | Summary: Refine receptor autophosphorylation to the measured tyrosine chemistry. Reason: The broad autophosphorylation assertion is sound. Human ALK is a tyrosine kinase and its activation-loop tyrosine phosphorylation is established independently of the abstract-only 1997 source. Use the specific peptidyl-tyrosine autophosphorylation term while preserving each original source object and ordinary relationship field. Proposed replacements: peptidyl-tyrosine autophosphorylation Supporting Evidence: PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. Reactome:R-HSA-201521 Trans-phosphorylation of the three tyrosine residues in the activation (Y1278, Y1282 and Y1283) after ligand binding causes a conformational change that relieves autoinhibition of the kinase |
| GO:0046777 protein autophosphorylation | IDA PMID:9174053 ALK, the chromosome 2 gene locus altered by the t(2;5) in no... | MODIFY | Summary: Refine receptor autophosphorylation to the measured tyrosine chemistry. Reason: The broad autophosphorylation assertion is sound. Human ALK is a tyrosine kinase and its activation-loop tyrosine phosphorylation is established independently of the abstract-only 1997 source. Use the specific peptidyl-tyrosine autophosphorylation term while preserving each original source object and ordinary relationship field. Proposed replacements: peptidyl-tyrosine autophosphorylation Supporting Evidence: PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. Reactome:R-HSA-201521 Trans-phosphorylation of the three tyrosine residues in the activation (Y1278, Y1282 and Y1283) after ligand binding causes a conformational change that relieves autoinhibition of the kinase |
| GO:0046777 protein autophosphorylation | TAS PMID:19459784 Anaplastic lymphoma kinase: signalling in development and di... | MODIFY | Summary: Refine receptor autophosphorylation to the measured tyrosine chemistry. Reason: The broad autophosphorylation assertion is sound. Human ALK is a tyrosine kinase and its activation-loop tyrosine phosphorylation is established independently of the abstract-only 1997 source. Use the specific peptidyl-tyrosine autophosphorylation term while preserving each original source object and ordinary relationship field. Proposed replacements: peptidyl-tyrosine autophosphorylation Supporting Evidence: PMID:30061385 full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. Reactome:R-HSA-201521 Trans-phosphorylation of the three tyrosine residues in the activation (Y1278, Y1282 and Y1283) after ligand binding causes a conformational change that relieves autoinhibition of the kinase |
| GO:0048666 neuron development | TAS PMID:19459784 Anaplastic lymphoma kinase: signalling in development and di... | KEEP AS NON CORE | Summary: Retain neuronal development as a contextual receptor role. Reason: The cited review integrates neuronal expression and experimental vertebrate models; expression alone does not demonstrate the developmental step. Independent human-ALK cell differentiation, zebrafish functional studies and recent mouse oral sensory-neuron/taste-bud studies provide positive functional context. Mouse knockout innervation phenotypes are distinguished from adult inhibitor-induced neuronal loss; the recovered study explicitly allows INSR/IGF1R inhibition to contribute to the stronger drug phenotype. Supporting Evidence: PMID:26418745 FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK |
| GO:0050995 negative regulation of lipid catabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse neural ALK suppresses peripheral lipid mobilization in a defined physiological context. Reason: The term-specific mouse P97793 donor is traced through the MGI graph to PMID:32442405. Full primary Results show global and hypothalamic PVN Alk deletion increasing sympathetic adipose signaling and lipid mobilization, including conditional adult deletion controls. ALK performs a neural regulatory signaling role, not lipid hydrolysis. The ortholog inference is retained as contextual biology; human thinness associations do not themselves reproduce the mouse perturbation experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P97793 SUPPORTS TRANSFER Term-specific mouse Alk evidence recovered through the MGI comparative GO graph: PMID:32442405. Positive donor biology is retained with organismal/developmental scope; this is not a failure inferred from donor count. |
| GO:0050995 negative regulation of lipid catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse neural ALK suppresses peripheral lipid mobilization in a defined physiological context. Reason: The term-specific mouse P97793 donor is traced through the MGI graph to PMID:32442405. Full primary Results show global and hypothalamic PVN Alk deletion increasing sympathetic adipose signaling and lipid mobilization, including conditional adult deletion controls. ALK performs a neural regulatory signaling role, not lipid hydrolysis. The ortholog inference is retained as contextual biology; human thinness associations do not themselves reproduce the mouse perturbation experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P97793 SUPPORTS TRANSFER Term-specific mouse Alk evidence recovered through the MGI comparative GO graph: PMID:32442405. Positive donor biology is retained with organismal/developmental scope; this is not a failure inferred from donor count. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | UNDECIDED | Summary: The urinary-exosome detection requires the target-level proteomic evidence. Reason: The cached source is abstract-only, and the exact ALK peptide/target entry was not recovered from the original urinary-exosome supporting tables. Cell-surface receptor biology does not prove or refute vesicular recovery. No contamination claim or functional exosome role is inferred. |
| GO:0097009 energy homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the organismal energy-homeostasis role with mouse donor scope. Reason: The MGI graph resolves mouse P97793 evidence to PMID:32442405. Global and PVN-specific loss increases energy expenditure and protects against diet-induced obesity in mice; feeding efficiency and peripheral tissue controls distinguish a neural signaling mechanism. This is a justified physiological context of receptor activity, not evidence that every human tissue uses ALK for systemic energy balance. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P97793 SUPPORTS TRANSFER Term-specific mouse Alk evidence recovered through the MGI comparative GO graph: PMID:32442405. Positive donor biology is retained with organismal/developmental scope; this is not a failure inferred from donor count. |
| GO:0097009 energy homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the organismal energy-homeostasis role with mouse donor scope. Reason: The MGI graph resolves mouse P97793 evidence to PMID:32442405. Global and PVN-specific loss increases energy expenditure and protects against diet-induced obesity in mice; feeding efficiency and peripheral tissue controls distinguish a neural signaling mechanism. This is a justified physiological context of receptor activity, not evidence that every human tissue uses ALK for systemic energy balance. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P97793 SUPPORTS TRANSFER Term-specific mouse Alk evidence recovered through the MGI comparative GO graph: PMID:32442405. Positive donor biology is retained with organismal/developmental scope; this is not a failure inferred from donor count. |
| GO:1900006 positive regulation of dendrite development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ALK signaling supports dendrite maturation in a mouse hippocampal context. Reason: The mouse donor is traced to PMID:30497772. Original indexed Results/Figures 5–6 show newborn dentate-neuron Alk knockdown reducing dendrite growth and complexity, with PTN/ALK-dependent downstream signaling. These are mouse receptor-function experiments, not direct proof of PTN–ALK binding or a human in-vivo dendritic assay. The developmental context is retained without creating a separate molecular-function core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P97793 SUPPORTS TRANSFER Term-specific mouse Alk evidence recovered through the MGI comparative GO graph: PMID:30497772. Positive donor biology is retained with organismal/developmental scope; this is not a failure inferred from donor count. |
| GO:1900006 positive regulation of dendrite development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ALK signaling supports dendrite maturation in a mouse hippocampal context. Reason: The mouse donor is traced to PMID:30497772. Original indexed Results/Figures 5–6 show newborn dentate-neuron Alk knockdown reducing dendrite growth and complexity, with PTN/ALK-dependent downstream signaling. These are mouse receptor-function experiments, not direct proof of PTN–ALK binding or a human in-vivo dendritic assay. The developmental context is retained without creating a separate molecular-function core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P97793 SUPPORTS TRANSFER Term-specific mouse Alk evidence recovered through the MGI comparative GO graph: PMID:30497772. Positive donor biology is retained with organismal/developmental scope; this is not a failure inferred from donor count. |
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Download this section (compressed HTML)Q: Can purified human ALK receptor assemblies increase kinase activity through a separable noncovalent mechanism, distinguished from trans-autophosphorylation, sufficient for GO:0030298?
Q: Which exact ALK-containing complex, urinary-exosome target peptides and interaction-screen supporting-data entries underlie the source-limited assertions retained as UNDECIDED?
Q: What does the linked Oncogene 1997;15(23):2883 erratum correct in the original ALK report, and does it affect any assay interpretation?
Q: Which mouse hypothalamic energy-balance and neuronal-development mechanisms are conserved in normal human tissues, and how do ALKAL/heparin and indirect PTN–PTPRZ routes vary by cell context?
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