ALK 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. Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily. Expressed in brain and CNS. Also expressed in the small intestine and testis, but not in normal lymphoid cells. Note: This description may include information from UniProtKB.
Protein type: Alk family; EC; Kinase, protein; Membrane protein, integral; Oncoprotein; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group
Chromosomal Location of human Ortholog: 2p23.2-p23.1
Cellular Component:  plasma membrane; protein-containing complex; receptor complex
Molecular Function:  ATP binding; heparin binding; identical protein binding; NF-kappaB-inducing kinase activity; protein binding; protein tyrosine kinase activity; receptor signaling protein tyrosine kinase activator activity; transmembrane receptor protein tyrosine kinase activity
Biological Process:  adult behavior; energy homeostasis; hippocampus development; multicellular organism development; negative regulation of lipid catabolic process; neuron development; NIK/NF-kappaB signaling; peptidyl-tyrosine autophosphorylation; phosphorylation; positive regulation of dendrite development; positive regulation of kinase activity; positive regulation of MAPK cascade; positive regulation of NF-kappaB transcription factor activity; positive regulation of protein tyrosine kinase activity; protein autophosphorylation; regulation of apoptotic process; regulation of cell population proliferation; regulation of dopamine receptor signaling pathway; regulation of neuron differentiation; response to environmental enrichment; signal transduction; swimming behavior; transmembrane receptor protein tyrosine kinase signaling pathway
Disease: Neuroblastoma, Susceptibility To, 3
Reference #:  Q9UM73 (UniProtKB)
Alt. Names/Synonyms: ALK; ALK receptor tyrosine kinase; ALK tyrosine kinase receptor; Anaplastic lymphoma kinase; anaplastic lymphoma receptor tyrosine kinase; CD246; CD246 antigen; mutant anaplastic lymphoma kinase; NBLST3
Gene Symbols: ALK
Molecular weight: 176,442 Da
Basal Isoelectric point: 6.67  Predict pI for various phosphorylation states
CST Pathways:  Tyrosine Kinases & Substrates
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  CCLE  |  Wikipedia  |  neXtProt  |  Protein Atlas  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene