Protein kinase C-delta is a target of B-cell antigen receptor signaling

Immunol Lett. 1999 Aug 3;69(2):259-67. doi: 10.1016/s0165-2478(99)00090-5.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / enzymology*
  • B-Lymphocytes / immunology
  • Biological Transport / drug effects
  • Enzyme Activation / drug effects
  • Estrenes / pharmacology
  • Humans
  • Ionomycin / pharmacology
  • Isoenzymes / physiology*
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Phosphatidylinositol Diacylglycerol-Lyase
  • Phosphorylation
  • Protein Kinase C / physiology*
  • Protein Kinase C-delta
  • Protein Processing, Post-Translational
  • Pyrrolidinones / pharmacology
  • Receptors, Antigen, B-Cell / physiology*
  • Signal Transduction / physiology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured
  • Type C Phospholipases / metabolism

Substances

  • Estrenes
  • Isoenzymes
  • Pyrrolidinones
  • Receptors, Antigen, B-Cell
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Phorbol 12,13-Dibutyrate
  • Ionomycin
  • Prkcd protein, mouse
  • PRKCD protein, human
  • Protein Kinase C
  • Protein Kinase C-delta
  • Type C Phospholipases
  • Phosphatidylinositol Diacylglycerol-Lyase
  • Tetradecanoylphorbol Acetate