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PMID: 10675325 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A truncated isoform of the PP2A B56 subunit promotes cell motility through paxillin phosphorylation.

The EMBO journal ·Vol. 19 ·No. 4 ·2000-02-15 ·Pages 562-71

Ito A, Kataoka TR, Watanabe M, Nishiyama K, Mazaki Y, Sabe H, Kitamura Y, Nojima H

Abstract

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 (Deltagamma1) of the B56gamma1 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 B56gamma subunits by co-immunoprecipitation. B56gamma1 co-localized with paxillin at focal adhesions, suggesting a role for this isoform in targeting PP2A to paxillin. In this regard, Deltagamma1 behaved similarly to B56gamma1. However, the Deltagamma1-containing PP2A heterotrimer was insufficient for the dephosphorylation of paxillin. Transfection with Deltagamma1 enhanced paxillin phosphorylation on serine residues and recruitment into focal adhesions, and cell spreading with an actin network. In addition, Deltagamma1 rendered F10 cells as highly metastatic as BL6 cells. These results suggest that mutations in PP2A regulatory subunits may cause malignant progression.

MeSH Terms
3T3 Cells Animals Base Sequence COS Cells Cell Cycle/physiology Cell Movement/physiology Cytoskeletal Proteins/metabolism Cytoskeleton/metabolism DNA Primers/genetics Gene Expression Melanoma, Experimental/genetics,metabolism,secondary Mice Molecular Sequence Data Paxillin Phosphoprotein Phosphatases/chemistry,genetics,metabolism Phosphoproteins/metabolism Phosphorylation Protein Structure, Quaternary RNA, Messenger/genetics,metabolism RNA, Neoplasm/genetics,metabolism Serine/metabolism Tumor Cells, Cultured
Chemicals
Cytoskeletal Proteins DNA Primers Paxillin Phosphoproteins Pxn protein, mouse RNA, Messenger RNA, Neoplasm Serine Phosphoprotein Phosphatases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Ito A
Department of Pathology, Medical School.
Kataoka T R
Watanabe M
Nishiyama K
Mazaki Y
Sabe H
Kitamura Y
Nojima H
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.4.562
Published
2000-02-15
Pages
562-71
Language
English
Region
England
NLM ID
8208664
PMCID
PMC305594
Subset
IM
Databases
GENBANK
AB026817, U59418
External Links
PubMed source DOI: 10.1093/emboj/19.4.562 PMC Full Text View journal details
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