Association of pp60c-src with biliary glycoprotein (CD66a), an adhesion molecule of the carcinoembryonic antigen family downregulated in colorectal carcinomas.
CD66a, also known as 'biliary glycoprotein (BGP)', is the human homologue of a cell adhesion molecule (CAM) of the rat (Cell-CAM). CD66a, which belongs to the carcinoembryonic antigen family and the immunoglobulin superfamily, is expressed in cells of myeloid and epithelial origin. The cytoplasmic domain of the major isoform of CD66a (CD66acyt) contains two tyrosine residues in amino acid motifs potentially interacting with protein tyrosine kinases of the Src family. Here we provide evidence that CD66a is associated with pp60c-src. From membrane fractions of granulocytes and the colonic cell line HT29, phosphokinase activity was co-immunoprecipitated with CD66a when monoclonal CD66 antibodies or an antiserum against the recombinant cytoplasmic domain of CD66a were used. From the dissociated immunecomplexes, a phosphokinase of M(r) 60,000 was reprecipitated using antibodies against pp60c-src. In vitro, the recombinant cytoplasmic domain was a substrate and binding partner of pp60c-src. Phosphopeptides corresponding to the tyrosine containing amino acid sequences of CD66acyt activated the kinase activity of pp60c-src to a greater extent than a phosphopeptide containing Tyr527 from the SH2-binding regulatory domain of pp60c-src. The down-regulation of CD66a in about 80% of colorectal carcinomas may contribute to a dysregulation of pp60c-src in colorectal cancer.
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000235:genetics; D002277:Carcinoma / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D006023:Glycoproteins / Q000378:metabolism*; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011233:Precipitin Tests; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D015398:Signal Transduction; D018909:src Homology Domains
D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D010748:Phosphopeptides; D019000:Phosphotyrosine; D016392:Proto-Oncogene Proteins pp60(c-src)