Integrin-dependent tyrosine phosphorylation and growth regulation by Vav

Ilana Yron*, Marcel Deckert, Mitchell E. Reff, Anil Munshi, Martin A. Schwartz, Amnon Altman

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    29 Scopus citations

    Abstract

    The proto-oncogene product p95Vav (Vav) undergoes rapid phosphorylation on tyrosine following stimulation of the T or B cell antigen receptor, and in response to a variety of other cell surface stimuli. Vav contains, among other, a guanine nucleotide exchange factor domain with homology to the Rho/Rac/CDC42 exchange protein Db1. It has been recently shown that Vav is functionally linked to small GTPases of the Rho family suggesting that it is an activator of Rho GTPases and may participate in regulation of cytoskeletal organization. The present study shows that cell adhesion to fibronectin triggers rapid phosphorylation of Vav on tyrosine in Vav-transfected CHO cells and in Jurkat T cells. Vav phosphorylation is strongly dependent on adhesion and is mediated by β1 integrins. Furthermore, Vav overexpression enhances the adhesion-dependent increase in the rate and extent of phosphorylation on focal adhesion kinase and paxillin, and the formation of stress fibers and lamellipodia. In addition, there is a marked increase in the amount of Vav localized to the triton-insoluble fraction following 1 h of incubation on FN. Finally, Vav increases the growth rate of the cells in an adhesion-dependent manner. Our results strongly implicate Vav as a mediator of integrin signal transduction.

    Original languageEnglish
    Pages (from-to)1-11
    Number of pages11
    JournalCell Adhesion and Communication
    Volume7
    Issue number1
    DOIs
    StatePublished - 1999

    Funding

    FundersFunder number
    National Institutes of HealthR01 GM27214
    National Institute of General Medical SciencesR01GM050819
    Israel Science Foundation

      Keywords

      • Growth regulation
      • Integrin signaling
      • Vav

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