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Description

ALK tyrosine kinase receptor (UniProt: Q9UM73, also known as EC: 2.7.10.1, Anaplastic lymphoma kinase, CD246) is encoded by the ALK gene (Gene ID: 238) in human. ALK tyrosine kinase receptor is a single-pass type I membrane protein that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the development and function of the nervous system. It is predominantly expressed in the central nervous system, intestine, and testis. It acts as a receptor for ligands pleiotrophin (PTN) and midkine (MDK). It is activated and homodimerizes by ligand-binding and subsequent phosphorylation. 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. It is inactivated through dephosphorylation by receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) in the absence of any stimulation by a ligand. A chromosomal aberration involving ALK has been reported in non-Hodgkin lymphoma where the kinase is constitutively activated. Another chromosomal aberration involving ALK has also been linked with anaplastic large-cell lymphoma (ALCL). ALK tyrosine kinase receptor is synthesized with a signal peptide (aa 1-18), which is subsequently cleaved off in the mature form. ALK tyrosine kinase receptor consists of an extracellular domain (aa 19-1038), a transmembrane domain (aa 1039-1059), and a cytoplasmic domain (aa 1060-1620).