ALK Recombinant Rabbit mAb (SDT-3284)

Anaplastic lymphoma kinase (ALK), also designated CD246, is a single-pass transmembrane receptor tyrosine kinase of the insulin-receptor superfamily that is normally expressed at highest levels in the developing and adult nervous system, where it regulates neuronal differentiation, axon guidance and cognition; the 1620-aa glycoprotein presents an N-terminal extracellular region containing two MAM domains and an LDL-A module for ligand binding, a single hydrophobic transmembrane segment and a C-terminal cytoplasmic kinase domain that, upon ligand-induced dimerization, undergoes trans-autophosphorylation and triggers RAS–MAPK, PI3K–AKT and JAK–STAT signaling cascades controlling cell proliferation and survival. Chromosomal translocations (most famously t(2;5)(p23;q35) producing NPM1–ALK), inversions (EML4–ALK in non-small-cell lung cancer) or activating point mutations cause constitutive kinase activity, driving malignant transformation in anaplastic large-cell lymphoma, subsets of NSCLC, neuroblastoma and inflammatory myofibroblastoma, making the oncoprotein a validated therapeutic target for small-molecule inhibitors such as crizotinib, alectinib and lorlatinib.