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doi: 10.1242/10.1242/jcs.00122

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Journal of Cell Science 115, 4399-4411 (2002)
doi: 10.1242/jcs.00122

Commentary

Move over protein kinase C, you've got company: alternative cellular effectors of diacylglycerol and phorbol esters

Nils Brose1,* and Christian Rosenmund2

1 Abteilung Molekulare Neurobiologie, Max-Planck-Institut für Experimentelle Medizin, D-37075 Göttingen, Germany
2 Abteilung Membranbiophysik, Max-Planck-Institut für Biophysikalische Chemie, D-37077 Göttingen, Germany

* Author for correspondence (e-mail: brose{at}em.mpg.de)

Diacylglycerol is an essential second messenger in mammalian cells. The most prominent intracellular targets of diacylglycerol and of the functionally analogous phorbol esters belong to the protein kinase C (PKC) family. However, at least five alternative types of high-affinity diacylglycerol/phorbol-ester receptor are known: chimaerins, protein kinase D, RasGRPs, Munc13s and DAG kinase {gamma}. Recent evidence indicates that these have functional roles in diacylglycerol second messenger signalling in vivo and that several cellular processes depend on these targets rather than protein kinase C isozymes. These findings contradict the still prevalent view according to which all diacylglycerol/phorbol-ester effects are caused by the activation of protein kinase C isozymes. RasGRP1 (in Ras/Raf/MEK/ERK signalling) and Munc13-1 (in neurotransmitter secretion) are examples of non-PKC diacylglycerol/phorbol-ester receptors that mediate diacylglycerol and phorbol-ester effects originally thought to be caused by PKC isozymes. In the future, pharmacological studies on PKC must be complemented with alternative experimental approaches to allow the separation of PKC-mediated effects from those caused by alternative targets of the diacylglycerol second messenger pathway. The examples of RasGRP1 and Munc13-1 show that detailed genetic analyses of C1-domain-containing non-PKC diacylglycerol/phorbol-ester receptors in mammals are ideally suited to achieve this goal.

Key words: Protein kinase C, Phorbol ester, Munc13, Secretion, Synapse


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The folly of phorbol ester

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