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Protein kinase D. A selective target for antigen receptors and a downstream target for protein kinase C in
S A Matthews1, E Rozengurt, D Cantrell
1Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.
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.
Insights
Diacylglycerol-regulated protein kinase Cs (PKCs) control protein kinase D (PKD) activity following antigen receptor signaling in immune cells. This reveals a PKC signaling network amplifying immune responses.
Area of Science:
- Immunology
- Cell Signaling
- Molecular Biology
Background:
- Protein kinase Cs (PKCs) are activated by antigen receptors in lymphocytes.
- Proximal targets for PKCs in antigen receptor-mediated responses are not well understood.
Purpose of the Study:
- To define the role of diacylglycerol-regulated PKC isoforms in controlling protein kinase D (PKD) activity in T cells, B cells, and mast cells.
- To elucidate the signaling pathway linking antigen receptor activation to PKD activity.
Main Methods:
- Biochemical assays to measure kinase activity.
- Genetic studies in immune cells (T cells, B cells, mast cells).
- Analysis of signaling pathways following antigen receptor stimulation.
Main Results:
- Antigen receptor activation of PKD is a rapid and sustained response in T cells, B cells, and mast cells.
- Antigen receptor activation of PKD requires the activity of classical/novel PKCs.
- PKC activity alone is sufficient to induce PKD activity, bypassing antigen receptor signals.
Conclusions:
- Diacylglycerol-regulated PKC isoforms play a critical role in controlling PKD activity downstream of antigen receptors.
- A signaling network exists between upstream PKCs and PKD that amplifies and disseminates antigen receptor signals.
- This study establishes a novel signaling pathway involving the PKC superfamily in immune cell activation.