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Structural Insights into Phospholipase C- β Function

2013; American Society for Pharmacology and Experimental Therapeutics; Volume: 84; Issue: 4 Linguagem: Inglês

10.1124/mol.113.087403

1521-0111

Angeline M. Lyon, J.J.G. Tesmer,

Cellular transport and secretion

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 β subfamily is of particular interest given its prominent role in cardiovascular and neuronal signaling and its regulation by G protein–coupled receptors, as PLC β is the canonical downstream target of the heterotrimeric G protein G α q . However, this is not the only mechanism regulating PLC β activity. Extensive structural and biochemical evidence has revealed regulatory roles for autoinhibitory elements within PLC β , G βγ , 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 β .