Regulation of phosphoinositide kinases in T cells. Evidence that phosphatidylinositol 3-kinase is not a substrate for T cell antigen receptor- regulated tyrosine kinases

S. G. Ward (Lead / Corresponding author), K. Reif, S. Ley, M. J. Fry, M. D. Waterfield, D. A. Cantrell

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    44 Citations (Scopus)

    Abstract

    A phosphoinositide kinase that can phosphorylate phosphatidylinositol (PtdIns) is present in 4G10 monoclonal antibody (mAb) phosphotyrosine immunoprecipitates isolated from T cells activated via the T cell antigen receptor (TCR)·CD3 complex. This PtdIns kinase is not the PtdIns 3-kinase that associates with activated protein tyrosine kinases in fibroblasts, since Western blotting and immunoprecipitation experiments with antibodies specific for the p85α subunit of the PtdIns 3-kinase indicate that this polypeptide is not immunoprecipitated by the 4G10 mAb from TCR·CD3-activated Jurkat cells. Moreover, immunoprecipitated PtdIns 3-kinase isolated from T cells with p85 antibodies is inhibited when PtdIns is presented in Nonidet P-40, whereas the PtdIns kinase activity present in 4G10 mAb phosphotyrosine immunoprecipitates is enhanced in the presence of Nonidet P-40. In vitro kinase assays of PtdIns 3-kinase immunoprecipitated with p85 antibodies from T cells indicate that it associates with a serine kinase that can phosphorylate a p85 polypeptide. However, no protein tyrosine kinase activity capable of tyrosine phosphorylating p85 in vitro associates with p85α immunoprecipitates in quiescent or TCR·CD3-activated T cells. These data suggest that the TCR·CD3 complex does not regulate PtdIns 3-kinase activity by a mechanism that involves protein tyrosine kinases.

    Original languageEnglish
    Pages (from-to)23862-23869
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume267
    Issue number33
    Publication statusPublished - 1 Dec 1992

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