Rho-dependent and -independent tyrosine phosphorylation of focal adhesion kinase, paxillin and p130(Cas) mediated by Ret kinase

Hideki Murakami, Toshihide Iwashita, Naoya Asai, Yosuke Iwata, Shuh Narumiya, Masahide Takahashi

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69 Citations (Scopus)


Glial cell line-derived neurotrophic factor (GDNF) signals through a unique receptor system that includes Ret receptor tyrosine kinase and a glycosyl-phosphatidylinositol-linked cell surface protein. In the present study, we have identified several proteins in neuroblastoma cells that are phosphorylated on tyrosine in response to GDNF. The phosphorylated proteins include focal adhesion kinase (FAK), paxillin and Crk-associated substrate, p130(Cas), all of which are known to be associated with focal adhesions. Of these, paxillin and p130(Cas) interacted with Crk proteins in GDNF-treated neuroblastoma cells. GDNF also induced reorganization of the actin cytoskelton. Tyrosine phosphorylation of FAK, paxillin and p130(Cas) was inhibited by cytochalasin D or two specific inhibitors of phosphatidylinositol-3' kinase (PI-3' kinase), wortmannin and LY294002, indicating that their tyrosine phosphorylation depends on the formation of actin stress fiber and activation of PI-3' kinase. In addition, phosphorylatioa of FAK but not of paxillin and p130(Cas) was markedly impaired by the Clostridium botulinum C3 exoenzyme that specifically ADP-ribosylates and inactivates Rho. These results suggested the presence of Rho-dependent and -independent signaling pathways downstream of PI-3' kinase that mediate tyrosine phosphorylation of FAK, paxillin and p130(Cas) through Ret kinase.

Original languageEnglish
Pages (from-to)1975-1982
Number of pages8
Issue number11
Publication statusPublished - 18-03-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research


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