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A truncated isoform of the PP2A B56 subunit promotes cell motility through paxillin phosphorylation
Author(s) -
Ito Akihiko,
Kataoka Tatsuki R.,
Watanabe Masafumi,
Nishiyama Kazutaka,
Mazaki Yuichi,
Sabe Hisataka,
Kitamura Yukihiko,
Nojima Hiroshi
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.4.562
Subject(s) - paxillin , protein phosphatase 2 , phosphorylation , biology , focal adhesion , transfection , gene isoform , dephosphorylation , microbiology and biotechnology , protein subunit , serine , immunoprecipitation , cancer research , phosphatase , cell culture , biochemistry , gene , genetics
Both F10 and BL6 sublines of B16 mouse melanoma cells are metastatic after intravenous injection, but only BL6 cells are metastatic after subcutaneous injection. Retrotransposon insertion was found to produce an N‐terminally truncated form (Δγ1) of the B56γ1 regulatory subunit isoform of protein phosphatase (PP) 2A in BL6 cells, but not in F10 cells. We found an interaction of paxillin with PP2A C and B56γ subunits by co‐immunoprecipitation. B56γ1 co‐localized with paxillin at focal adhesions, suggesting a role for this isoform in targeting PP2A to paxillin. In this regard, Δγ1 behaved similarly to B56γ1. However, the Δγ1‐containing PP2A heterotrimer was insufficient for the dephosphorylation of paxillin. Transfection with Δγ1 enhanced paxillin phosphorylation on serine residues and recruitment into focal adhesions, and cell spreading with an actin network. In addition, Δγ1 rendered F10 cells as highly metastatic as BL6 cells. These results suggest that mutations in PP2A regulatory subunits may cause malignant progression.