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