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© The Rockefeller University Press, 0021-9525/1999//1511 $5.00
The Journal of Cell Biology, Volume 145, Number 7, , 1999 1511-1520

Regular Articles

The Dynamics of Protein Kinase B Regulation during B Cell Antigen Receptor Engagement



Emmanuelle Astoul*, Sandra Watton{ddagger}, and Doreen Cantrell*

* Lymphocyte Activation Laboratory, {ddagger} Signal Transduction Laboratories, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom

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 Fc{gamma}RIIB, 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 Fc{gamma}RIIB prevents membrane targeting of PKB. The Fc{gamma}RIIB 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 Fc{gamma}RIIB on the BCR/PKB response.

Key Words: Akt/PKB • phosphatidylinositol 3-kinase • GSK3 • B cell antigen receptor • Fc{gamma}RIIb

Abbreviations used in this paper: BCR, B cell antigen receptor; GFP, green fluorescent protein; GSK3, glycogen synthase kinase 3; PH, plextrin homology; PI3K, phosphatidylinositol 3-kinase; PKB, protein kinase B.

E. Astoul is supported by the European Community Training and Mobility of Researchers Program (ERBFMICT 960518).


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