Phosphatidylinositol 3-kinase signals activate a selective subset of Rac/Rho-dependent effector pathways

Karin Reif (Lead / Corresponding author), Catherine D. Nobes, George Thomas, Alan Hall, Doreen A. Cantrell

    Research output: Contribution to journalArticle

    238 Citations (Scopus)

    Abstract

    Background: Phosphatidylinositol 3'-hydroxyl kinase (PI 3-kinase) is activated by many growth factor receptors and is thought to exert its cellular functions through the elevation of phosphatidylinositol (3,4,5)- triphosphate levels in the cell. PI 3-kinase is required for growth-factor induced changes of the actin cytoskeleton which are mediated by the GTPases Rac and Rho. Recently, a role for Rac and Rho in regulating gene transcription has become evident. 

    Results: Here, we show that membrane targeting of the p110 catalytic subunit, but not the p85 regulatory subunit, of PI 3-kinase generates a constitutively active enzyme that allows us to assess the relative contribution of PI 3-kinase activation to a particular cellular response. Expression of this active PI 3-kinase induced actin reorganization in the form of Rac-mediated lamellipodia and focal complexes, and Rho-mediated stress fibres and focal adhesions. However, expression of active PI 3-kinase did not induce the Ras/Rac/Rho signalling pathways that regulate gene transcription controlled by the c-fos promoter, the c-fos serum response element or the transcription factors Elk-1 and AP-1. 

    Conclusions: Our results demonstrate that PI 3-kinase induces a selective subset of cellular responses, but is not sufficient to stimulate the full repertoire of Rac- or Rho-mediated responses.

    Original languageEnglish
    Pages (from-to)1445-1455
    Number of pages11
    JournalCurrent Biology
    Volume6
    Issue number11
    DOIs
    Publication statusPublished - 1 Nov 1996

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