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Journal of Cell Science 115, e2302-e2302 (2002)
Copyright © 2002 The Company of Biologists Limited


In this issue

The folly of phorbol ester


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 on p. 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 T cell receptors to MAP kinase activation in thymocytes. Brose and Rosenmund conclude that susceptibility to phorbol esters does not alone constitute a test for PKC involvement and discuss additional criteria that should be satisfied.


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Related articles in JCS:

Move over protein kinase C, you've got company: alternative cellular effectors of diacylglycerol and phorbol esters
Nils Brose and Christian Rosenmund
JCS 2002 115: 4399-4411. [Abstract] [Full Text]  




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