title: Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes.
abstract: p120 was originally identified as a substrate of pp60src and several receptor tyrosine kinases, but its function is not known. Recent studies revealed that this protein shows homology to a group of proteins, beta-catenin/Armadillo and plakoglobin (gamma-catenin), which are associated with the cell adhesion molecules cadherins. In this study, we examined whether p120 is associated with E-cadherin using the human carcinoma cell line HT29, as well as other cell lines, which express both of these proteins. When proteins that copurified with E-cadherin were analyzed, not only alpha-catenin, beta-catenin, and plakoglobin but also p120 were detected. Conversely, immunoprecipitates of p120 contained E-cadherin and all the catenins, although a large subpopulation of p120 was not associated with E-cadherin. Analysis of these immunoprecipitates suggests that 20% or less of the extractable E-cadherin is associated with p120. When p120 immunoprecipitation was performed with cell lysates depleted of E-cadherin, beta-catenin was no longer coprecipitated, and the amount of plakoglobin copurified was greatly reduced. This finding suggests that there are various forms of p120 complexes, including p120/E-cadherin/beta-catenin and p120/E-cadherin/plakoglobin complexes; this association profile contrasts with the mutually exclusive association of beta-catenin and plakoglobin with cadherins. When the COOH-terminal catenin binding site was truncated from E-cadherin, not only beta-catenin but also p120 did not coprecipitate with this mutated E-cadherin. Immunocytological studies showed that p120 colocalized with E-cadherin at cell-cell contact sites, even after non-ionic detergent extraction. Treatment of cells with hepatocyte growth factor/scatter factor altered the level of tyrosine phosphorylation of p120 as well as of beta-catenin and plakoglobin. These results suggest that p120 associates with E-cadherin at its COOH-terminal region, but the mechanism for this association differs from that for the association of beta-catenin and plakoglobin with E-cadherin, and thus, that p120, whose function could be modulated by growth factors, may play a unique role in regulation of the cadherin-catenin adhesion system.
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Shibamoto
authors.forename: M
authors.initials: M
authors.lastname: Hayakawa
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: T
authors.initials: T
authors.lastname: Hori
authors.forename: K
authors.initials: K
authors.lastname: Miyazawa
authors.forename: N
authors.initials: N
authors.lastname: Kitamura
authors.forename: K R
authors.initials: KR
authors.lastname: Johnson
authors.forename: M J
authors.initials: MJ
authors.lastname: Wheelock
authors.forename: N
authors.initials: N
authors.lastname: Matsuyoshi
authors.forename: M
authors.initials: M
authors.lastname: Takeichi
mesh_terms: D001665:Binding Sites; D015820:Cadherins / Q000302:isolation & purification / Q000378:metabolism*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000302:isolation & purification / Q000378:metabolism*; D002451:Cell Compartmentation; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003902:Detergents; D005455:Fluorescent Antibody Technique; D006801:Humans; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D051176:beta Catenin; D000095002:Delta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D003902:Detergents; D010750:Phosphoproteins; D015534:Trans-Activators; D051176:beta Catenin; D014443:Tyrosine; D000095002:Delta Catenin