WD repeat and coiled-coil-containing protein
protein complex oligomerization
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 <i>ALK</i> 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 <i>ALK</i> gene and chromosome 2, open reading frame 44 (<i>C2orf44</i>), a gene of unknown function. As a first step in understanding the oncogenic properties of this fusion protein, <i>C2orf44</i> 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 <i>ALK-C2orf44</i> gene fusion, WDCP imposes an oligomeric structure on ALK that results in constitutive kinase activation and signaling.