Pharmacologic modulation of protein kinase C isozymes: the role of RACKs and subcellular localisation.
Protein kinase C (PKC) isozymes are highly homologous kinases and several different isozymes can be present in a cell. Each isozyme is likely to mediate unique functions, but pharmacological tools to explore their isozyme-specific roles have not been available until recently. In this review, we describe the development and application of isozyme-selective inhibitors of PKC. The identification of these inhibitors stems from the observation that PKC isozymes are each localised to unique subcellular locations following activation. Inhibitors of this isozyme-unique localisation have been shown to act as selective inhibitors of the functions of individual isozymes. The identification of isozyme-specific inhibitors should allow the exploration of individual PKC isozyme function in a wide range of cell systems.
Csukai
M
M
Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305-5332, USA.
Mochly-Rosen
D
D
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000502:physiology*; D013347:Subcellular Fractions / Q000201:enzymology; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D011493:Protein Kinase C