Molecular characterization of WDCP, a novel fusion partner for the anaplastic lymphoma tyrosine kinase ALK.

Anaplastic lymphoma kinase (ALK) is a member of the receptor tyrosine kinase superfamily. The gene is a site of frequent mutation and chromosomal rearrangement in various types of human cancers. A novel chromosomal translocation was recently identified in human colorectal cancer between the gene and chromosome 2, open reading frame 44 (), a gene of unknown function. As a first step in understanding the oncogenic properties of this fusion protein, cDNA was cloned and the encoded protein was characterized, which was designated as WD repeat and coiled coil containing protein (WDCP). A C-terminal proline-rich segment in WDCP was shown to mediate binding to the Src homology 3 domain of the Src family kinase hematopoietic cell kinase (Hck). Co-expression with Hck lead to tyrosine phosphorylation of WDCP. Chromatographic fractionation of WDCP-containing lysates indicates that the protein exists as an oligomer in mammalian cells. These results suggest that, in the context of the gene fusion, WDCP imposes an oligomeric structure on ALK that results in constitutive kinase activation and signaling.