Introduction

Anaplastic lymphoma kinase, (also known as ALK, CD246 antigen, Ki 1 antigen, ALK tyrosine kinase receptor) is a member of the receptor tyrosine kinase (RTK) family. These proteins are essential for the transmission of extra-cellular signals to the interior of the cell and play essential roles in cellular activities including cell-cycle progression, differentiation, migration, reaction to stress, and survival.

ALK has been ascribed a role in neural development in humans, rodents, birds, Drosophila and Caenorhabditis elegans, as well as being necessary for gut muscle development in Drosophila. While many of the signaling pathways associated with ALK are common to other RTKs, the normal function of ALK has yet to be completely understood.

In common with other RTKs, ALK is frequently afected by chromosomal abnormalities, e.g. point mutations and translocations, resulting in the production of oncogenic ALK proteins with constitutively activated TK domains. Importantly, in contrast to other RTKs, oncogenic ALK proteins are present in hematopoietic as well as non-hematopoietic tumors. Indeed, the identiication of nucleophosmin (NPM)-ALK led to the recognition of the tumor entity ALK-positive anaplastic large cell lymphoma (ALCL). Much of the information concerning the signaling pathways of ALK has been elucidated from the study of the NPM-ALK fusion protein.