Protein Kinase D: A Selective Target for Antigen Receptors and a Downstream Target for Protein Kinase C in Lymphocytes

doi:10.1084/jem.191.12.2075

Published online 12 June 2000.

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© The Rockefeller University Press, 0022-1007/2000/6/2075/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 12, June 19, 2000 2075-2082

Original Article

Protein Kinase D: A Selective Target for Antigen Receptors and a Downstream Target for Protein Kinase C in Lymphocytes

Sharon A. Matthews^a, Enrique Rozengurt^b, and Doreen Cantrell^a
^a Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom
^b Department of Medicine, University of California Los Angeles School of Medicine and Molecular Biology Institute, Los Angeles, California 90095-1786

Correspondence to: Doreen Cantrell, Lymphocyte Activation Laboratory, Rm. 106, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. Tel:44-020-7269-3307 Fax:44-020-7269-2831 E-mail:d.cantrell{at}icrf.icnet.uk.

Protein kinase Cs (PKCs) are activated by antigen receptorsin lymphocytes, but little is known about proximal targets forPKCs in antigen receptor–mediated responses. In this report,we define a role for diacylglycerol-regulated PKC isoforms incontrolling the activity of the serine/threonine kinase proteinkinase D (PKD; also known as PKCµ) in T cells, B cells,and mast cells. Antigen receptor activation of PKD is a rapidand sustained response that can be seen in T cells activatedvia the T cell antigen receptor, B cells activated via the Bcell antigen receptor, and in mast cells triggered via the high-affinityreceptor for IgE (Fc ${epsilon}$ R1). Herein, we show that antigen receptoractivation of PKD requires the activity of classical/novel PKCs.Moreover, PKC activity is sufficient to bypass the requirementfor antigen receptor signals in the induction of PKD activity.These biochemical and genetic studies establish a role for antigenreceptor–regulated PKC enzymes in the control of PKD activity.Regulation of PKD activity through upstream PKCs reveals a signalingnetwork that exists between different members of the PKC superfamilyof kinases that can operate to amplify and disseminate antigenreceptor signals generated at the plasma membrane.

Key Words: antigen receptor, diacylglycerol, protein kinase C, proteinkinase D

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