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Stem Cells, Vol. 16, No. 3, 178-192, May 1998
© 1998 AlphaMed Press

Concise Reviews

New Perspectives on PKC{theta}, a Member of the Novel Subfamily of Protein Kinase C

Nahum Mellera, Amnon Altmanb, Noah Isakova

a Department of Microbiology and Immunology, Faculty of Health Sciences, and the Cancer Research Center, Ben Gurion University of the Negev, Beer Sheva, Israel;
b Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California, USA

Key Words. PKC • T cell activation • Cell signaling • Isoenzymes • Protein kinase

Dr. Noah Isakov, Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105, Israel.

Members of the protein kinase C (PKC) family of serine/threonine protein kinases have been implicated in numerous cellular responses in a large variety of cell types. Expression patterns of individual members and differences in their cofactor requirements and potential substrate specificity suggest that each isoenzyme may be involved in specific regulatory processes. The PKC{theta} isoenzyme exhibits a relatively restricted expression pattern with high protein levels found predominantly in hematopoietic cells and skeletal muscle. PKC{theta} was found to be expressed in T, but not B lymphocytes, and to colocalize with the T-cell antigen receptor (TCR) at the site of contact between the antigen-responding T cell and the antigen-presenting cell (APC). Colocalization of PKC{theta} with the TCR was selective for this isoenzyme and occurred only upon antigen-mediated responses leading to T-cell activation and proliferation. PKC{theta} was found to be involved in the regulation of transcriptional activation of early-activation genes, predominantly AP-1, and its cellular distribution and activation were found to be regulated by the 14-3-3 protein. Other findings indicated that PKC{theta} can associate with the HIV negative factor (Nef) protein, suggesting that altered regulation of PKC{theta} by Nef may contribute to the T-cell impairments that are characteristic of infection by HIV. PKC{theta} is expressed at relatively high levels in skeletal muscle, where it is suggested to play a role in signal transduction in both the developing and mature neuromuscular junction. In addition, PKC{theta} appears to be involved in the insulin-mediated response of intact skeletal muscle, as well as in experimentally induced insulin resistance of skeletal muscle. Further studies suggest that PKC{theta} is expressed in endothelial cells and is involved in multiple processes essential for angiogenesis and wound healing, including the regulation of cell cycle progression, formation and maintenance of actin cytoskeleton, and formation of capillary tubes. Here, we review recent progress in the study of PKC{theta} and discuss its potential role in various cellular responses.




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