Human ALK/CD246 Antibody

ALK (Anaplastic Lymphoma Kinase; also CD246) is a 200-220 kDa member of the Insulin receptor subfamily, tyrosine kinase family, protein kinase superfamily of proteins.  It shows restricted expression, being limited to select sympathetic and sensory neurons, endothelial cells and tumor cells.  Although activation of ALK appears to induce cell proliferation, the exact ligand(s) for ALK is unknown.  In a temporally-regulated context, midkine has been suggested to bind to ALK, and ionic Zn has been reported to activate ALK cytoplasmically.  Mature human ALK is a 1602 amino acid (aa) type I transmembrane glycoprotein (SwissProt #:Q9UM73).  It contains a 1020 aa extracellular region (aa 19-1038) that contains one protein-protein MAM domain (aa 264-427), an LDL receptor class A region (aa 437-473), a second MAM domain (aa 480-631) and one utilized phosphorylation site at Ser211.  This is accompanied by a long 561 aa cytoplasmic domain that possesses a protein kinase domain (aa 1116-1392) plus eleven utilized Tyr phosphorylation sites.  There is one potential splice variant that contains a four aa insert after Glu549.  There is also an 80 kDa soluble product that arises from cleavage of the extracellular domain.  Although a third 140 kDa product is frequently seen in SDS-Page, its structural basis is unclear.  Almost 20 distinct ALK fusion products arise from gene translocations involving multiple intracellular molecules.  These seem to involve blocks of aa starting between aa 1050-1060 and continuing to aa 1620.  Over aa 19-1038, human ALK shares 88% aa sequence identity with mouse ALK.