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PMID: 10922062 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Paxillin alpha and Crk-associated substrate exert opposing effects on cell migration and contact inhibition of growth through tyrosine phosphorylation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 16 ·2000-08-01 ·Pages 9076-81

Yano H, Uchida H, Iwasaki T, Mukai M, Akedo H, Nakamura K, Hashimoto S, Sabe H

Abstract

Protein tyrosine phosphorylation accompanies and is essential for integrin signaling. We have shown that tyrosine phosphorylation of paxillin alpha and Crk-associated substrate (p130(Cas)) is a prominent event on integrin activation in normal murine mammary gland epithelial cells. Tyrosine phosphorylation of p130(Cas) has been demonstrated to facilitate cell migration. We show here that tyrosine phosphorylation of paxillin alpha acts to reduce haptotactic cell migrations as well as transcellular invasive activities in several different experimental cell systems, whereas tyrosine phosphorylation of p130(Cas) exerts opposing effects to those of paxillin alpha. Each of the phosphorylation-null mutants acts as a dominant negative for each phenotype. Moreover, we found that overexpression of paxillin alpha reduced the cell saturation density of normal murine mammary gland cells, whereas overexpression of p130(Cas) increased it. These effects also seemed to depend on tyrosine phosphorylation events. Cell growth rates and morphologies at growing phases were not significantly altered, nor were cells transformed. Addition of epidermal growth factor increased saturation density of the paxillin alpha-overexpressing cells, whereas no further increment was observed in p130(Cas)-overexpressing cells. We propose that tyrosine phosphorylation of paxillin alpha and p130(Cas) exerts opposing effects on several integrin-mediated cellular events, possibly through different signaling pathways.

MeSH Terms
Animals Cell Division/physiology Cell Line Cell Movement/physiology Crk-Associated Substrate Protein Cytoskeletal Proteins/physiology Paxillin Phosphoproteins/physiology Phosphorylation Proteins Rats Retinoblastoma-Like Protein p130 Signal Transduction Tyrosine/metabolism
Chemicals
Bcar1 protein, rat Crk-Associated Substrate Protein Cytoskeletal Proteins Paxillin Phosphoproteins Proteins Pxn protein, rat Retinoblastoma-Like Protein p130 Tyrosine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Yano H
Department of Molecular Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
Uchida H
Iwasaki T
Mukai M
Akedo H
Nakamura K
Hashimoto S
Sabe H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.97.16.9076
Published
2000-08-01
Pages
9076-81
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC16824
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.97.16.9076 PMC Full Text View journal details
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