title: Molecular characterization of WDCP, a novel fusion partner for the anaplastic lymphoma tyrosine kinase ALK.
abstract: Anaplastic lymphoma kinase (ALK) is a member of the receptor tyrosine kinase superfamily. TheALKgene 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 theALKgene and chromosome 2, open reading frame 44 (C2orf44), a gene of unknown function. As a first step in understanding the oncogenic properties of this fusion protein,C2orf44cDNA 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 theALK-C2orf44gene fusion, WDCP imposes an oligomeric structure on ALK that results in constitutive kinase activation and signaling.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yokoyama
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
authors.forename: W Todd
authors.initials: WT
authors.lastname: Miller
keywords: Src homology 3 domain; anaplastic lymphoma kinase; chromosomal translocation; hematopoietic cell kinase