Structural Insights into Phospholipase C-β Function

Phospholipase C (PLC) enzymes convert phosphatidylinositol-4,5-bisphosphate into the second messengers diacylglycerol and inositol-1,4,5-triphosphate. The production of these molecules promotes the release of intracellular calcium and activation of protein kinase C, which results in profound cellular changes. The PLC beta subfamily is of particular interest given its prominent role in cardiovascular and neuronal signaling and its regulation by G protein-coupled receptors, as PLC beta is the canonical downstream target of the heterotrimeric G protein G alpha q. However, this is not the only mechanism regulating PLC beta activity. Extensive structural and biochemical evidence has revealed regulatory roles for autoinhibitory elements within PLC beta, G beta gamma, small molecular weight G proteins, and the lipid membrane itself. Such complex regulation highlights the central role that this enzyme plays in cell signaling. A better understanding of the molecular mechanisms underlying the control of its activity will greatly facilitate the search for selective small molecule modulators of PLC beta.