Protein kinase D. A selective target for antigen receptors and a downstream target for protein kinase C in lymphocytes

J Exp Med. 2000 Jun 19;191(12):2075-82. doi: 10.1084/jem.191.12.2075.

Abstract

Protein kinase Cs (PKCs) are activated by antigen receptors in lymphocytes, but little is known about proximal targets for PKCs in antigen receptor-mediated responses. In this report, we define a role for diacylglycerol-regulated PKC isoforms in controlling the activity of the serine/threonine kinase protein kinase D (PKD; also known as PKC mu) in T cells, B cells, and mast cells. Antigen receptor activation of PKD is a rapid and sustained response that can be seen in T cells activated via the T cell antigen receptor, B cells activated via the B cell antigen receptor, and in mast cells triggered via the high-affinity receptor for IgE (FcepsilonR1). Herein, we show that antigen receptor activation of PKD requires the activity of classical/novel PKCs. Moreover, PKC activity is sufficient to bypass the requirement for antigen receptor signals in the induction of PKD activity. These biochemical and genetic studies establish a role for antigen receptor-regulated PKC enzymes in the control of PKD activity. Regulation of PKD activity through upstream PKCs reveals a signaling network that exists between different members of the PKC superfamily of kinases that can operate to amplify and disseminate antigen receptor signals generated at the plasma membrane.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Diglycerides / metabolism
  • Interleukin-2 / pharmacology
  • Isoenzymes / metabolism*
  • Lymphocytes / immunology*
  • Mast Cells / immunology
  • Mice
  • Protein Kinase C / metabolism*
  • Receptor Aggregation
  • Receptors, Antigen / metabolism*
  • Signal Transduction
  • T-Lymphocytes / immunology

Substances

  • Diglycerides
  • Interleukin-2
  • Isoenzymes
  • Receptors, Antigen
  • protein kinase D
  • Protein Kinase C