Journal
PHARMACOLOGICAL RESEARCH
Volume 55, Issue 6, Pages 537-544Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2007.04.009
Keywords
PKC theta; T cell; signal transduction; TCR; CD28
Categories
Funding
- NCI NIH HHS [R01 CA035299, R01 CA035299-25, CA35299] Funding Source: Medline
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Protein kinase C theta (PKC theta) is a member of the novel, Ca2+-independent PKC subfamily, which plays an important and non-redundant role in several aspects of T cell biology. Much progress has been accomplished in understanding the function of PKC theta in the immune system and its unique translocation to the immunological synapse in Ag-stimulated T lymphocytes. Biochemical and genetic approaches revealed that PKC theta is required for the activation of mature T cells as well as for their survival. Mutation of the PKC theta gene leads to impaired receptor-induced stimulation of the transcription factors AP-L NF-kappa B and NFAT, which results in defective T cell activation, and to aberrant expression of apoptosis-related proteins, resulting in poor T cell survival. Furthermore, PKC theta-deficient mice display defects in the differentiation of T helper subsets, particularly in Th2- and Th17-mediated inflammatory responses. Therefore, PKC theta is a critical enzyme that regulates T cell function at multiple stages, and it represents an attractive drug target for allergic and autoimmune diseases. (C) 2007 Elsevier Ltd. All rights reserved.
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