Abstract
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 language | English |
|---|---|
| Pages (from-to) | 9076-9081 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 97 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - 2000 Aug 1 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
- General
Cite this
Paxillin α and Crk-associated substrate exert opposing effects on cell migration and contact inhibition of growth through tyrosine phosphorylation. / Yano, Hajime; Uchida, Hiroshi; Iwasaki, Teruo; Mukai, Mutsuko; Akedo, Hitoshi; Nakamura, Kuniaki; Hashimoto, Shigeru; Sabe, Hisataka.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 16, 01.08.2000, p. 9076-9081.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Paxillin α and Crk-associated substrate exert opposing effects on cell migration and contact inhibition of growth through tyrosine phosphorylation
AU - Yano, Hajime
AU - Uchida, Hiroshi
AU - Iwasaki, Teruo
AU - Mukai, Mutsuko
AU - Akedo, Hitoshi
AU - Nakamura, Kuniaki
AU - Hashimoto, Shigeru
AU - Sabe, Hisataka
PY - 2000/8/1
Y1 - 2000/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034255237&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034255237&partnerID=8YFLogxK
U2 - 10.1073/pnas.97.16.9076
DO - 10.1073/pnas.97.16.9076
M3 - Article
C2 - 10922062
AN - SCOPUS:0034255237
VL - 97
SP - 9076
EP - 9081
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 16
ER -