ALK/p80

Anaplastic lymphoma kinase (ALK) is a novel receptor protein-tyrosine kinase having a putative transmembrane domain and an extracellular domain. The 2:5 chromosomal translocation occurs in most anaplastic large-cell non-Hodgkin's lymphomas arising from activated T lymphocytes. This rearrangement was shown to fuse the NPM nucleolar phosphoprotein gene on chromosome 5q35 to a previously unidentified protein tyrosine kinase gene, ALK, on chromosome 2p23. In the predicted hybrid protein, the amino terminus of NPM is linked to the catalytic domain of ALK. Immunoblotting with anti-ALK antibody shows that ALK is highly expressed in the neonatal brain. Also expressed in the small intestine, testis and brain, but not in normal lymphoid cells, ALK shows greatest sequence similarity to the insulin receptor subfamily of kinases. Unscheduled expression of the truncated ALK may contribute to malignant transformation in these lymphomas.