Pharmacological regulation of network kinetics by protein kinase C localization.
Protein kinase C (PKC) is a conserved family of 11 serine/threonine kinases. Most cell types express multiple members of the family. Because the catalytic sites are homologous, and able to accommodate a broad range of substrates in vitro, specificity in function is dependent on subcellular localization of each isozyme in each cell type. Physiological stimulation can result in major changes in localization of individual PKC isozymes, mediated through binding to specific anchoring proteins. We describe data demonstrating that disruption of such translocations of PKC isozymes by pharmacological agents, peptides, or antibodies, causes profound effects on T cell functions. The pharmacological opportunity provided by distinct kinetic properties of complex assembly is also discussed.
Mochly-Rosen
D
D
Dept. of Molecular Pharmacology, Stanford Medical School, CA 94305-5332, USA.
Kauvar
L M
LM
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000201:enzymology*
D016207:Cytokines; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011948:Receptors, Antigen, T-Cell; D011493:Protein Kinase C