Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes

Sayumi Shibamoto, Makio Hayakawa, Kenji Takeuchi, Takamitsu Hori, Keiji Miyazawa, Naomi Kitamura, Keith R. Johnson, Margaret J. Wheelock, Norihisa Matsuyoshi, Masatoshi Takeichi, Fumiaki Ito

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237 Scopus citations

Abstract

p120 was originally identified as a substrate of pp60(src) and several receptor tyrosine kinases, but its function is not known. Recent studies revealed that this protein shows homology to a group of proteins, β- catenin/Armadillo and plakoglobin (γ-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 α-catenin, β-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, β-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/β-catenin and p120/E-cadherin/plakoglobin complexes; this association profile contrasts with the mutually exclusive association of β- catenin and plakoglobin with cadherins. When the COOH-terminal catenin binding site was truncated from E-cadherin, not only β-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 β-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 β- 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.

Original languageEnglish (US)
Pages (from-to)949-957
Number of pages9
JournalJournal of Cell Biology
Volume128
Issue number5
DOIs
StatePublished - Mar 1 1995

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Shibamoto, S., Hayakawa, M., Takeuchi, K., Hori, T., Miyazawa, K., Kitamura, N., Johnson, K. R., Wheelock, M. J., Matsuyoshi, N., Takeichi, M., & Ito, F. (1995). Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes. Journal of Cell Biology, 128(5), 949-957. https://doi.org/10.1083/jcb.128.5.949