New insights into the regulation of protein kinase C and novel phorbol ester receptors.
Protein kinase C (PKC), a family of related serine-threonine kinases, is a key player in the cellular responses mediated by the second messenger diacylglycerol (DAG) and the phorbol ester tumor promoters. The traditional view of PKCs as DAG/phospholipid-regulated proteins has expanded in the last few years by three seminal discoveries. First, PKC activity and maturation is controlled by autophosphorylation and transphosphorylation mechanisms, which includes phosphorylation of PKC isozymes by phosphoinositide-dependent protein kinases (PDKs) and tyrosine kinases. Second, PKC activity and localization are regulated by direct interaction with different types of interacting proteins. Protein-protein interactions are now recognized as important mechanisms that target individual PKCs to different intracellular compartments and confer selectivity by associating individual isozymes with specific substrates. Last, the discovery of novel phorbol ester receptors lacking kinase activity allows us to speculate that some of the biological responses elicited by phorbol esters or by activation of receptors coupled to elevation in DAG levels could be mediated by PKC-independent pathways.
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Department of Neurology, Ernest Gallo Clinic and Research Center, University of California San Francisco, San Francisco, California 94110-3518, USA. dorit@itsa.ucsf.edu
Kazanietz
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D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004075:Diglycerides / Q000378:metabolism*; D004789:Enzyme Activation; D007527:Isoenzymes / Q000378:metabolism; D010703:Phorbol Esters / Q000378:metabolism*; D011485:Protein Binding; D011493:Protein Kinase C / Q000145:classification / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D015290:Second Messenger Systems; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004075:Diglycerides; D007527:Isoenzymes; D010703:Phorbol Esters; D011955:Receptors, Drug; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D020703:ras GTPase-Activating Proteins; D011493:Protein Kinase C; D020830:rac1 GTP-Binding Protein