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Updated: Jul 2, 2026

Detection of Phospholipase C Activity in the Brain Homogenate from the Honeybee
Published on: September 14, 2018
General and versatile autoinhibition of PLC isozymes
Stephanie N Hicks1, Mark R Jezyk, Svetlana Gershburg
1Department of Pharmacology, The University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Abstract:
Phospholipase C (PLC) isozymes are directly activated by heterotrimeric G proteins and Ras-like GTPases to hydrolyze phosphatidylinositol 4,5-bisphosphate into the second messengers diacylglycerol and inositol 1,4,5-trisphosphate. Although PLCs play central roles in myriad signaling cascades, the molecular details of their activation remain poorly understood. As described here, the crystal structure of PLC-beta2 illustrates occlusion of the active site by a loop separating the two halves of the catalytic TIM barrel. Removal of this insertion constitutively activates PLC-beta2 without ablating its capacity to be further stimulated by classical G protein modulators. Similar regulation occurs in other PLC members, and a general mechanism of interfacial activation at membranes is presented that provides a unifying framework for PLC activation by diverse stimuli.
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