Protein kinase C isozyme selective peptides--a current view of what they tell us about location and function of isozymes in the heart.
The identification of protein kinase C isozymes in distinct localities within the cell has led to the suggestion that each isozyme mediates a unique function. This has necessitated the development of methodologies that are capable of assigning specific function to an isozyme. For many years the location of individual isozymes in a particulate fraction was used to correlate specific isozymes with cellular function. More recently over-expression of selective isozymes and genetic knockouts have provided tissue-specific and developmentally regulated information on function. It is now known that specific proteins act as isozyme selective receptors for activated C kinase (RACKs) which determine subcellular localization of specific isozymes. As a result, peptides have been designed from the interaction site between the isozyme and its RACK that prevent the binding of isozymes to their respective RACKs. This has allowed the modulation of function of individual isozymes. This review will examine the development of the peptides as isozyme selective inhibitors or activators of PKC and its impact on understanding the role of isozymes in cellular function in the healthy and diseased heart. The possible development of isozyme-specific drugs for therapeutic use will be discussed.
Hool
Livia C
LC
Physiology M311, School of Biomedical and Chemical Sciences, The University of Western Australia, Stirling Highway, Crawley, WA, 6009, Australia. lhool@cyllene.uwa.edu.au
D006321:Heart / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D009206:Myocardium / Q000201:enzymology*; D010455:Peptides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000502:physiology
D007527:Isoenzymes; D010455:Peptides; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D011493:Protein Kinase C