Activation of protein kinase C (PKC) by diacylglycerol generated through hydrolysis of phosphatidylinositol 4,5-bisphosphate is a classic signal transduction mechanism. Indeed, cell biologists and pharmacologists have over the years used the diacylglycerol analogue phorbol ester to implicate PKC in a wide variety of processes. Recent work, however, indicates that diacylglycerol and phorbol ester have additional targets, such as chimaerins, the Ras activator RasGRP and the vesicle-priming protein Munc-13. In a Commentary onp. 4399, Nils Brose and Christian Rosenmund review the evidence for such non-PKC targets. These proteins each contain the diacylglycerol-binding C1 domain and function in processes in which PKCs were previously implicated. Release of neurotransmitter from hippocampal neurons, for example, is regulated by phorbol ester, but since neurons expressing a Munc-13 C1-domain mutant cannot respond to phorbol ester the target must be Munc-13. Similar work indicates that RasGRP — and not PKC — couples...

You do not currently have access to this content.