Activation and tyrosine phosphorylation of protein kinase C δ in response to B cell antigen receptor stimulation

Activation of the B cell through antigen receptor (BCR) crosslinking is known to initiate a prominent tyrosine kinase cascade and lipid second messenger production through the activation of phospholipase Cy and phosphatidylinositol 3' kinase. In this study, we demonstrate that protein kinase C delta (PKC delta) responds to crosslinking of the BCR by becoming activated and tyrosine phosphorylated within 30 s of stimulation. PKC delta activation was dependent primarily on phosphatidylinositol 3' kinase, and this in turn was dependent on an upstream tyrosine phosphorylation event. Inhibition of PKC delta activation by blocking phosphatidylinositol 3' kinase was also accompanied by a decrease in its tyrosine phosphorylation, suggesting that PKC delta must be activated in order to become tyrosine phosphorylated. Inhibition of phospholipase C activation had an insignificant effect on the activation of PKC delta, however it attenuated the tyrosine phosphorylation of PKC delta. This suggests a distinct role for phospholipase C in the regulation of PKC delta. This report describes a role for PKC delta in response to the combined signals originated by the BCR. (C) 2000 Elsevier Science Ltd. All rights reserved.