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J. Biol. Chem. 280 (2): 1438-1447

© 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

Phospholipase C{beta}2 Binds to and Inhibits Phospholipase C{delta}1*

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Yuanjian Guo, Mario Rebecchi, , and Suzanne Scarlata{ddagger}

Department of Physiology and Biophysics and the Department of Anesthesiology, State University of New York, Stony Brook, New York 11794-8661

Abstract: Phospholipase C{beta} (PLC{beta}) isoforms, which are under the control of G{alpha}q and G{beta}{gamma} subunits, generate Ca2+ signals induced by a broad array of extracellular agonists, whereas PLC{delta} isoforms depend on a rise in cytosolic Ca2+ for their activation. Here we find that PLC{beta}2 binds strongly to PLC{delta}1 and inhibits its catalytic activity in vitro and in living cells. In vitro, this PLC complex can be disrupted by increasing concentrations of free G{beta}{gamma} subunits. Such competition has consequences for signaling, because in HEK293 cells PLC{beta}2 suppresses elevated basal [Ca2+] and inositol phosphates levels and the sustained agonist-induced elevation of Ca2+ levels caused by PLC{delta}1. Also, expression of both PLCs results in a synergistic release of [Ca2+] upon stimulation in A10 cells. These results support a model in which PLC{beta}2 suppresses the basal catalytic activity of PLC{delta}1, which is relieved by binding of G{beta}{gamma} subunits to PLC{beta}2 allowing for amplified calcium signals.

Received for publication July 7, 2004. Revision received October 25, 2004.

* This work was supported by National Institutes of Health Grants GM53132 (to S. S.) and GM60376 (to M. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


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The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1.

{ddagger} To whom correspondence to should be addressed. Tel.: 631-444-3071; Fax: 631-444-3432; E-mail: Suzanne.Scarlata{at}sunysb.edu.

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