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Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7843-6.

Selective interaction of the C2 domains of phospholipase C-beta1 and -beta2 with activated Galphaq subunits: an alternative function for C2-signaling modules.

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Department of Physiology and Biophysics, State University of New York, Stony Brook, NY 11794-8661, USA.


Phospholipase C (PLC)-beta1 and PLC-beta2 are regulated by the Gq family of heterotrimeric G proteins and contain C2 domains. These domains are Ca2+-binding modules that serve as membrane-attachment motifs in a number of signal transduction proteins. To determine the role that C2 domains play in PLC-beta1 and PLC-beta2 function, we measured the binding of the isolated C2 domains to membrane bilayers. We found, unexpectedly, that these modules do not bind to membranes but they associate strongly and specifically to activated [guanosine 5'-[gamma-thio]triphosphate (GTP[gammaS])-bound] Galphaq subunits. The C2 domain of PLC-beta1 effectively suppressed the activation of the intact isozyme by Galphaq(GTP[gammaS]), indicating that the C2-Galphaq interaction may be physiologically relevant. C2 affinity for Galphaq(GTP[gammaS]) was reduced when Galphaq was deactivated to the GDP-bound state. Binding to activated Galphai1 subunits or to Gbetagamma subunits was not detected. Also, Galphaq(GTP[gammaS]) failed to associate with the C2 domain of PLC-delta, an isozyme that is not activated by Galphaq. These results indicate that the C2 domains of PLC-beta1 and PLC-beta2 provide a surface to which Galphaq subunits can dock, leading to activation of the native protein.

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