Protein kinase C-delta is a target of B-cell antigen receptor signaling.
Protein kinase C (PKC) enzymes have been implicated as key intermediates in B-cell antigen receptor (BCR) signaling. Each of the 11 PKC isoforms may phosphorylate different substrates and regulate different cellular processes. In this report we show that PKC-delta (PKC-delta) is a target of BCR signaling. BCR engagement increased the amount of PKC-delta in the membrane-enriched particulate fraction of B-cells, suggesting that BCR activates PKC-delta. BCR ligation also caused substantial tyrosine phosphorylation of PKC-delta. We show that activation of phospholipase C by BCR is necessary for both PKC-delta membrane localization and tyrosine phosphorylation. In contrast, phorbol esters which mimic the action of diacylglycerol could recruit PKC-delta to cellular membranes but did not induce tyrosine phosphorylation of PKC-delta. These data suggest a model in which phospholipase C-dependent production of diacylglycerol recruits PKC-delta to cellular membranes where it is then phosphorylated by BCR-activated tyrosine kinases.
Barbazuk
S M
SM
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
Gold
M R
MR
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D001692:Biological Transport / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007527:Isoenzymes / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D051745:Protein Kinase C-delta; D011499:Protein Processing, Post-Translational; D011760:Pyrrolidinones / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D004963:Estrenes; D007527:Isoenzymes; D011760:Pyrrolidinones; D011947:Receptors, Antigen, B-Cell; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; C497259:Prkcd protein, mouse; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D013755:Tetradecanoylphorbol Acetate