Identification of a new catenin: the tyrosine kinase substrate p120cas associates with E-cadherin complexes.
p120cas is a tyrosine kinase substrate implicated in ligand-induced receptor signaling through the epidermal growth factor, platelet-derived growth factor, and colony-stimulating factor receptors and in cell transformation by Src. Here we report that p120 associates with a complex containing E-cadherin, alpha-catenin, beta-catenin, and plakoglobin. Furthermore, p120 precisely colocalizes with E-cadherin and catenins in vivo in both normal and Src-transformed MDCK cells. Unlike beta-catenin and plakoglobin, p120 has at least four isoforms which are differentially expressed in a variety of cell types, suggesting novel means 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 were not disrupted. Association of p120 with the cadherin machinery indicates that both Src and receptor tyrosine kinases cross talk with proteins important for cadherin-mediated cell adhesion. These results also strongly suggest a role for p120 in cell adhesion.
Reynolds
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AB
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Daniel
J
J
McCrea
P D
PD
Wheelock
M J
MJ
Wu
J
J
Zhang
Z
Z
D016475:3T3 Cells; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000302:isolation & purification*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003598:Cytoskeletal Proteins / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000302:isolation & purification* / Q000378:metabolism; D019000:Phosphotyrosine; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D015534:Trans-Activators; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D051176:beta Catenin; D000095002:Delta Catenin
D000911:Antibodies, Monoclonal; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D010750:Phosphoproteins; D015534:Trans-Activators; D051176:beta Catenin; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D000095002:Delta Catenin