Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK.
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ALK: a tyrosine kinase of the ALK family. Plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. Translocated and expressed as a fusion protein in anaplastic lymphoma. About one third of large-cell lymphomas are caused by a t(2;5)(p23;q35) translocation that fuses ALK to nucleophosmin (NPM1A). Other cases caused by fusions of ALK to moesin, non-muscle myosin heavy chain 9, clathrin heavy chain and other genes. Several fusions also seen in inflammatory myofibroblastic tumors, and expression has been briefly noted in a range of tumors
Protein type: Alk family; EC 220.127.116.11; Kinase, protein; Membrane protein, integral; Oncoprotein; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group
Cellular Component: axon; integral to plasma membrane; plasma membrane; protein complex
Molecular Function: protein binding; protein-tyrosine kinase activity; transmembrane receptor protein tyrosine kinase activity
Biological Process: adult behavior; brain development; hippocampus development; nervous system development; phosphorylation; protein amino acid autophosphorylation; regulation of cell proliferation; regulation of dopamine receptor signaling pathway; response to stress
Probable tyrosine-protein kinase receptor which regulates the dauer/non-dauer developmental decision probably by controlling daf-3 transcriptional activity in parallel or together with the TGF-beta pathway (PubMed:11063683, PubMed:18674914). Regulates integration of conflicting sensory cues in AIA interneurons (PubMed:21414922). May act as a receptor for hen-1 (PubMed:18674914, PubMed:21414922).
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