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Publication Abstract from PubMed

Transmembrane signals initiated by a broad range of extracellular stimuli converge on nodes that regulate phospholipase C (PLC)-dependent inositol lipid hydrolysis for signal propagation. We describe how heterotrimeric guanine nucleotide-binding proteins (G proteins) activate PLC-betas and in turn are deactivated by these downstream effectors. The 2.7-angstrom structure of PLC-beta3 bound to activated Galpha(q) reveals a conserved module found within PLC-betas and other effectors optimized for rapid engagement of activated G proteins. The active site of PLC-beta3 in the complex is occluded by an intramolecular plug that is likely removed upon G protein-dependent anchoring and orientation of the lipase at membrane surfaces. A second domain of PLC-beta3 subsequently accelerates guanosine triphosphate hydrolysis by Galpha(q), causing the complex to dissociate and terminate signal propagation. Mutations within this domain dramatically delay signal termination in vitro and in vivo. Consequently, this work suggests a dynamic catch-and-release mechanism used to sharpen spatiotemporal signals mediated by diverse sensory inputs.

Kinetic Scaffolding Mediated by a Phospholipase C-{beta} and Gq Signaling Complex.,Waldo GL, Ricks TK, Hicks SN, Cheever ML, Kawano T, Tsuboi K, Wang X, Montell C, Kozasa T, Sondek J, Harden TK Science. 2010 Nov 12;330(6006):974-80. Epub 2010 Oct 21. PMID:20966218^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.