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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.R800045-JLR200 on November 24, 2008

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Journal of Lipid Research, Vol. 50, S243-S248, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Signaling

Phospholipase C isozymes as effectors of Ras superfamily GTPases

T. Kendall Harden1,*,{dagger}, Stephanie N. Hicks* and John Sondek*,{dagger},§

* Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599
{dagger} Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599
§ Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599

This work was supported by National Institutes of Health Grant GM-57391 (T.K.H. and J.S.) and a Ruth L. Kirschstein National Research Service Award fellowship F32GM074411 (S.N.H.).

Published, JLR Papers in Press, November 24, 2008.

1 To whom correspondence should be addressed. e-mail: tkh{at}med.unc.edu


ABSTRACT

The physiological effects of many extracellular stimuli are initiated through receptor-promoted activation of phospholipase C and inositol lipid signaling pathways. The historical view that phospholipase C-promoted signaling primarily occurs through activation of heterotrimeric G proteins or tyrosine kinases has expanded in recent years with the realization that at least three different mammalian phospholipase C isozymes are directly activated by members of the Ras superfamily of GTPases. Thus, Ras, Rap, Rac, and Rho GTPases all specifically regulate certain phospholipase C isozymes, and insight into the physiological significance of these signaling responses is beginning to accrue. High resolution three-dimensional structures of phospholipase C isozymes also are beginning to shed light on their mechanism of activation.

Supplementary key words inositol lipid signaling • Rac • Rho • Rap

Abbreviations: EF, elongation factor; GPCR, G-protein-coupled receptor; PH, pleckstrin homology; PLC, phospholipase C; RA, Ras-associating; TIM, triose phosphate isomerase


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JLR 50th Anniversary Collections
Anniversary Collection::Signaling



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