title: The E-cadherin complex contains the src substrate p120.
abstract: Using normal MDCK cells, and MDCK cells stably transfected with a temperature-sensitive viral src allele (pp60 ts-v-src), we have examined the composition and tyrosine phosphorylation of the E-cadherin complex. E-cadherin is a transmembrane calcium-dependent cell-cell adhesion molecule that is complexed with cytoplasmic proteins including alpha-catenin, beta-catenin, plakoglobin (gamma-catenin), and actin. We have identified two heterodimeric complexes which demonstrate that alpha-catenin interacts directly with beta-catenin, or with plakoglobin, in the absence of E-cadherin. beta-Catenin has previously been shown to bind directly to E-cadherin. We propose that E-cadherin associates with alpha-catenin, and thereby the actin cytoskeleton, via either beta-catenin or plakoglobin. We have further identified three new but related protein components of the E-cadherin complex, which are each cross-reactive by Western blot analysis to antibodies directed against p120, a phosphotyrosine substrate of src, and a phosphotyrosine, phosphoserine, and phosphothreonine substrate of growth factor-stimulated signaling pathways. Greater quantities of the p120-related proteins were found present in the E-cadherin immunoprecipitates of ts-src MDCK cells compared to normal MDCK cells, while two of the p120 cross-reactive species were significantly tyrosine phosphorylated in both normal and ts-src MDCK cells. The association of p120-related species with the E-cadherin complex adds them to our consideration of possible modulators of cadherin function. Likewise, the newly identified alpha-catenin-beta-catenin and alpha-catenin-plakoglobin dimers may have interesting biological properties, conceivably including the titration of catenins between cadherin and APC complexes.
authors.affiliation: Department of Growth and Development, University of California, San Francisco 94143, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Aghib
authors.forename: P D
authors.initials: PD
authors.lastname: McCrea
mesh_terms: D000818:Animals; D000906:Antibodies; D015820:Cadherins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D003208:Concanavalin A; D003598:Cytoskeletal Proteins / Q000302:isolation & purification / Q000378:metabolism; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D016391:Genes, src; D005822:Genetic Vectors; D007668:Kidney; D008715:Methionine / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src) / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D012190:Retroviridae; D015534:Trans-Activators; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D051178:alpha Catenin; D051176:beta Catenin
chemical_list: D000906:Antibodies; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D003208:Concanavalin A; D019000:Phosphotyrosine; D014443:Tyrosine; D008715:Methionine; D015688:Oncogene Protein pp60(v-src)