The dynamics of protein kinase B regulation during B cell antigen receptor engagement

Emmanuelle Astoul, Sandra Watton, Doreen Cantrell (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    113 Citations (Scopus)

    Abstract

    This study has used biochemistry and real time confocal imaging of green fluorescent protein (GFP)-tagged molecules in live cells to explore the dynamics of protein kinase B (PKB) regulation during B lymphocyte activation. The data show that triggering of the B cell antigen receptor (BCR) induces a transient membrane localization of PKB but a sustained activation of the enzyme; active PKB is found in the cytosol and nuclei of activated B cells. Hence, PKB has three potential sites of action in B lymphocytes; transiently after BCR triggering PKB can phosphorylate plasma membrane localized targets, whereas during the sustained B cell response to antigen, PKB acts in the nucleus and the cytosol. Membrane translocation of PKB and subsequent PKB activation are dependent on BCR activation of phosphatidylinositol 3-kinase (PI3K). Moreover, PI3K signals are both necessary and sufficient for sustained activation of PKB in B lymphocytes. However, under conditions of continuous PI3K activation or BCR triggering there is only transient recruitment of PKB to the plasma membrane, indicating that there must be a molecular mechanism to dissociate PKB from sites of PI3K activity in B cells. The inhibitory Fc receptor, the FcγRIIB, mediates vital homeostatic control of B cell function by recruiting an inositol 5 phosphatase SHIP into the BCR complex. Herein we show that coligation of the BCR with the inhibitory FcγRIIB prevents membrane targeting of PKB. The FcγRIIB can thus antagonize BCR signals for PKB localization and prevent BCR stimulation of PKB activity which demonstrates the mechanism for the inhibitory action of the FcγRIIB on the BCR/PKB response.

    Original languageEnglish
    Pages (from-to)1511-1520
    Number of pages10
    JournalJournal of Cell Biology
    Volume145
    Issue number7
    DOIs
    Publication statusPublished - 28 Jun 1999

    Keywords

    • Akt/PKB
    • B cell antigen receptor
    • FcγRIIb
    • GSK3
    • Phosphatidylinositol 3-kinase

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