Role of protein kinase C in T-cell antigen receptor regulation of p21ras: Evidence that two p21ras regulatory pathways coexist in T cells

Manuel Izquierdo, Julian Downward, Jonathan D. Graves, Doreen A. Cantrell

    Research output: Contribution to journalArticle

    133 Citations (Scopus)

    Abstract

    T-lymphocyte activation via the antigen receptor complex (TCR) results in accumulation of p21ras in the active GTP-bound state. Stimulation of protein kinase C (PKC) can also activate p21ras, and it has been proposed that the TCR effect on p21ras occurs as a consequence of TCR regulation of PKC. To test the role of PKC in TCR regulation of p21ras, a permeabilized cell system was used to examine TCR regulation of p21ras under conditions in which TCR activation of PKC was blocked, first by using a PKC pseudosubstrate peptide inhibitor and second by using ionic conditions that prevent phosphatidyl inositol hydrolysis and hence diacylglycerol production and PKC stimulation. The data show that TCR-induced p21ras activation is not mediated exclusively by PKC. Thus, in the absence of PKC stimulation, the TCR was still able to induce accumulation of p21ras-GTP complexes, and this stimulation correlated with an inactivation of p21ras GTPase-activating proteins. The protein tyrosine kinase inhibitor herbimycin could prevent the non-PKC-mediated, TCR-induced stimulation of p21ras. These data indicate that two mechanisms for p21ras regulation coexist in T cells: one PKC mediated and one not. The TCR can apparently couple to p21ras via a non-PKC-controlled route that may involve tyrosine kinases.

    Original languageEnglish
    Pages (from-to)3305-3312
    Number of pages8
    JournalMolecular and Cellular Biology
    Volume12
    Issue number7
    DOIs
    Publication statusPublished - 1 Jul 1992

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