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 PKCμ) 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 (FcεR1). 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.
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19 June 2000
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June 12 2000
Protein Kinase D: A Selective Target for Antigen Receptors and a Downstream Target for Protein Kinase C in Lymphocytes
Sharon A. Matthews,
Sharon A. Matthews
aLymphocyte Activation Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom
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Enrique Rozengurt,
Enrique Rozengurt
bDepartment of Medicine, University of California Los Angeles School of Medicine and Molecular Biology Institute, Los Angeles, California 90095-1786
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Doreen Cantrell
Doreen Cantrell
aLymphocyte Activation Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom
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Sharon A. Matthews
aLymphocyte Activation Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom
Enrique Rozengurt
bDepartment of Medicine, University of California Los Angeles School of Medicine and Molecular Biology Institute, Los Angeles, California 90095-1786
Doreen Cantrell
aLymphocyte Activation Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom
Abbreviations used in this paper: BCR, B cell antigen receptor; Erk, extracellular signal–regulated kinase; GFP, green fluorescent protein; PLC, phospholipase C; PKC, protein kinase C; PKD, protein kinase D; RBL, rat basophilic leukemia.
Received:
February 16 2000
Revision Requested:
April 12 2000
Accepted:
April 17 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 191 (12): 2075–2082.
Article history
Received:
February 16 2000
Revision Requested:
April 12 2000
Accepted:
April 17 2000
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Citation
Sharon A. Matthews, Enrique Rozengurt, Doreen Cantrell; Protein Kinase D: A Selective Target for Antigen Receptors and a Downstream Target for Protein Kinase C in Lymphocytes. J Exp Med 19 June 2000; 191 (12): 2075–2082. doi: https://doi.org/10.1084/jem.191.12.2075
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