Divergence and complexities in DAG signaling: Looking beyond PKC

Cheng Feng Yang, Marcelo G. Kazanietz

Research output: Contribution to journalReview articlepeer-review

187 Scopus citations

Abstract

For many years protein kinase C (PKC) has been the subject of extensive studies as a molecular target for the treatment of cancer and other diseases. To better define the role of PKC isozymes in the control of cell proliferation, survival and transformation, the examination of PKC-mediated signal transduction pathways by isozyme-specific intervention has become essential. However, issues related to the selectivity of activators and inhibitors of PKC isozymes, in addition to convoluted cross-talks between phorbol ester-regulated pathways, have greatly complicated our understanding of PKC-mediated responses. An additional level of complexity is provided by the fact diacylglycerol (DAG) signals can be transduced by phorbol ester receptors other than PKC. These receptors include chimaerins, RasGRPs, MUNC13s, PKD (PKCμ) and DAG kinases β and γ. Thus, it is conceivable that some of the effects that were originally attributed to PKC isozymes in response to phorbol esters might be mediated by PKC-independent pathways. A key issue for the design of novel therapeutic strategies that target PKC isozymes is a comprehensive analysis of isozyme-specific signal transduction pathways in different cell types and the development of pharmacological and molecular tools that can distinguish between the various PKC and 'non-PKC' phorbol ester receptors.

Original languageEnglish
Pages (from-to)602-608
Number of pages7
JournalTrends in Pharmacological Sciences
Volume24
Issue number11
DOIs
StatePublished - Nov 2003

Bibliographical note

Funding Information:
The laboratory of M.G.K. is supported by grants from NIH, ACS and DOD. C.Y. is supported by a postdoctoral fellowship from DOD.

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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