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

Hajime Yano, Hiroshi Uchida, Teruo Iwasaki, Mutsuko Mukai, Hitoshi Akedo, Kuniaki Nakamura, Shigeru Hashimoto, Hisataka Sabe

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Protein tyrosine phosphorylation accompanies and is essential for integrin signaling. We have shown that tyrosine phosphorylation of paxillin α 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 α 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 α. Each of the phosphorylation-null mutants acts as a dominant negative for each phenotype. Moreover, we found that overexpression of paxillin α 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 α-overexpressing cells, whereas no further increment was observed in p130(Cas)-overexpressing cells. We propose that tyrosine phosphorylation of paxillin α and p130(Cas) exerts opposing effects on several integrin-mediated cellular events, possibly through different signaling pathways.

Original languageEnglish
Pages (from-to)9076-9081
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number16
Publication statusPublished - 2000 Aug 1


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