Anaplastic lymphoma kinase: signalling in development and disease

RTKs (receptor tyrosine kinases) play important roles in cellular proliferation and different liation. In addition, RTKs reveal oncogenic potential when their kinase activities are constitutively enhanced by point mutation, amplification or rearrangement of the corresponding genes. The ALK (anaplastic iyniphoma kinase) RTK was originally identified as a member of tile insulin receptor subfamily of' Ill that acquires transforming capability when truncated and fused to NPM (nucleophosinin) in the til chromosomal rearrangement associated with ALCL (anaplastic large cell lyntiphoina). To date, many chromosomal rearrangements leading to enhanced ALK activity have been described and are implicated in a number-of cancer types. Recent reports of the EML4 (echinoderm microtubule-associated protein like 4)-ALK oncoprotein in NSCLC (non-small cell lung cancer), together with the identification of activating, point mutations in neuroblast have highlighted All as a significant player and target for drug development in cancer. In the present review we address the role of ALK in development and disease and discuss implications for the future.