ALK - ALK tyrosine kinase receptor - human protein (Function)
 
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ALK »  ALK tyrosine kinase receptor   [ EC 2.7.10.1 ]
 
Protein also known as:  Anaplastic lymphoma kinase; CD antigen CD246.
Gene name:  ALK
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Neuronal orphan 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.  
12
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
NF-kappaB-inducing kinase activitydefinition[GO:0004704]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
2
  • IntAct
Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • MGI
Transmembrane receptor protein tyrosine kinase activitydefinition[GO:0004714]  
2
  • UniProtKB
GO biological process 
Activation of MAPK activitydefinition[GO:0000187]  
1
  • UniProtKB
Cell proliferationdefinition[GO:0008283]  
1
  • UniProtKB
Neuron developmentdefinition[GO:0048666]  
1
  • UniProtKB
NIK/NF-kappaB signalingdefinition[GO:0038061]  
1
  • GOC
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
5
  • GOC
  • UniProtKB KW
  • EC 2 GO
  • InterPro 2 GO
Phosphorylationdefinition[GO:0016310]  
2
  • UniProtKB
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
1
  • UniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
3
  • UniProtKB
  • MGI
Regulation of apoptotic processdefinition[GO:0042981]  
1
  • UniProtKB
Signal transductiondefinition[GO:0007165]  
1
  • UniProtKB
Transmembrane receptor protein tyrosine kinase signaling pathwaydefinition[GO:0007169] silver  
1
  • InterPro 2 GO
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
2
  • UniProtKB
  • PROSITE-ProRule
It is regulated in the following manner
Activated by ligand-binding and subsequent phosphorylation. Inactivated through dephosphorylation by receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) when there is no stimulation by a ligand. Staurosporine, crizotinib and CH5424802 act as inhibitors of ALK kinase activity.  
4
  • UniProtKB
 
More information is available from:
 

Keywords

Molecular function 
Kinase  definition   [KW-0418]
Receptor  definition   [KW-0675]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Anaplastic_lymphoma_kinase
GenomeRNAi: 238
PRO: PR:Q9UM73
Chemistry
GuidetoPHARMACOLOGY: 1839