Protein kinase D. A selective target for antigen receptors and a downstream target for protein kinase C in lymphocytes.
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.
Matthews
S A
SA
Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.
Rozengurt
E
E
Cantrell
D
D
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D004075:Diglycerides / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D011940:Receptor Aggregation; D011946:Receptors, Antigen / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
D004075:Diglycerides; D007376:Interleukin-2; D007527:Isoenzymes; D011946:Receptors, Antigen; C089212:protein kinase D; D011493:Protein Kinase C