IDENTIFICATION OF A NEW CATENIN - THE TYROSINE KINASE SUBSTRATE P120(CAS) ASSOCIATES WITH E-CADHERIN COMPLEXES

p120(cas) is a tyrosine kinase substrate implicated in ligand-induced receptor signaling through the epidermal growth factor, platelet-deriv ed growth factor, and colony-stimulating factor receptors and in cell transformation by Src. Here we report that p120 associates with a comp lex containing E-cadherin, alpha-catenin, beta-catenin, and plakoglobi n. Furthermore, p120 precisely colocalizes with E-cadherin and catenin s in vivo in both normal and Src-transformed MDCK cells. Unlike beta-c atenin and plakoglobin, p120 has at least four isoforms which are diff erentially expressed in a variety of cell types, suggesting novel mean s of modulating cadherin activities in cells. In Src-transformed MDCK cells, p120, beta-catenin, and plakoglobin were heavily phosphorylated on tyrosine, but the physical associations between these proteins wer e not disrupted. Association of p120 with the cadherin machinery indic ates that both Src and receptor tyrosine kinases cross talk with prote ins important for cadherin-mediated cell adhesion. These results also strongly suggest a role for p120 in cell adhesion.