Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / enzymology*
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B-Lymphocytes / immunology
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Biological Transport / drug effects
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Enzyme Activation / drug effects
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Estrenes / pharmacology
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Humans
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Ionomycin / pharmacology
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Isoenzymes / physiology*
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Lymphocyte Activation / drug effects
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Mice
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Phorbol 12,13-Dibutyrate / pharmacology
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Phosphatidylinositol Diacylglycerol-Lyase
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Phosphorylation
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Protein Kinase C / physiology*
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Protein Kinase C-delta
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Protein Processing, Post-Translational
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Pyrrolidinones / pharmacology
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Receptors, Antigen, B-Cell / physiology*
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Signal Transduction / physiology*
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Tetradecanoylphorbol Acetate / pharmacology
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Tumor Cells, Cultured
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Type C Phospholipases / metabolism
Substances
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Estrenes
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Isoenzymes
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Pyrrolidinones
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Receptors, Antigen, B-Cell
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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Phorbol 12,13-Dibutyrate
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Ionomycin
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Prkcd protein, mouse
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PRKCD protein, human
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Protein Kinase C
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Protein Kinase C-delta
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Type C Phospholipases
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Phosphatidylinositol Diacylglycerol-Lyase
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Tetradecanoylphorbol Acetate