Activation and tyrosine phosphorylation of protein kinase C delta 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 Cgamma and phosphatidylinositol 3' kinase. In this study, we demonstrate that protein kinase C delta (PKCdelta) responds to crosslinking of the BCR by becoming activated and tyrosine phosphorylated within 30s of stimulation. PKC6 activation was dependent primarily on phosphatidylinositol 3' kinase, and this in turn was dependent on an upstream tyrosine phosphorylation event. Inhibition of PKCdelta activation by blocking phosphatidylinositol 3' kinase was also accompanied by a decrease in its tyrosine phosphorylation, suggesting that PKCdelta must be activated in order to become tyrosine phosphorylated. Inhibition of phospholipase C activation had an insignificant effect on the activation of PKCdelta, however it attenuated the tyrosine phosphorylation of PKCdelta. This suggests a distinct role for phospholipase C in the regulation of PKCdelta. This report describes a role for PKCdelta in response to the combined signals originated by the BCR.
Popoff
I J
IJ
Department of Biochemistry and Molecular Biology, University of Calgary, Alberta, Canada.
Deans
J P
JP
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003432:Cross-Linking Reagents; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism
D003432:Cross-Linking Reagents; D007527:Isoenzymes; D010455:Peptides; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta