ASSOCIATION OF PP60(C-SRC) WITH BILIARY GLYCOPROTEIN (CD66A), AN ADHESION MOLECULE OF THE CARCINOEMBRYONIC ANTIGEN FAMILY DOWN-REGULATED INCOLORECTAL CARCINOMAS

CD66a, also known as 'biliary glycoprotein (BGP)', is the human homolo gue of a cell adhesion molecule (CAM) of the rat (Cell-CAM). CD66a, wh ich belongs to the carcinoembryonic antigen family and the immunoglobu lin superfamily, is expressed in cells of myeloid and epithelial origi n. The cytoplasmic domain of the major isoform of CD66a (CD66a(cyt)) c ontains. two tyrosine residues in amino acid motifs potentially intera cting with protein tyrosine kinases of the Src family. Here we provide evidence that CD66a is associated with pp60(c-src). From membrane fra ctions of granulocytes and the colonic cell line HT29, phosphokinase a ctivity was co-immunoprecipitated with CD66a when monoclonal CD66 anti bodies or an antiserum against the recombinant cytoplasmic domain of C D66a were used. From the dissociated immunecomplexes, a phosphokinase of M(r) 60 000 was reprecipitated using antibodies against pp60(c-src) . In vitro, the recombinant cytoplasmic domain was a substrate and bin ding partner of pp60(c-src). Phosphopeptides corresponding to the tyro sine containing amino acid sequences of CD66a, activated the kinase ac tivity of pp60(c-src) to a greater extent than a phosphopeptide contai ning Tyr(527) from the SH2-binding regulatory domain of pp60(c-src). T he down-regulation of CD66a in about 80% of colorectal carcinomas may contribute to a dysregulation of pp60(c-src) in colorectal cancer.