The Mechanism of Regulation of -catalyzed Hydrolysis

Significance Statement: For certain cellular signaling processes, the background activity of signaling enzymes must be minimal and stimulus-dependent activation robust. Nowhere is this truer than in signaling by , whose activity regulates intracellular Ca , phosphorylation by Protein Kinase C, and the activity of numerous ion channels and membrane receptors. In this study we show how enzymes are regulated by two kinds of G proteins, and . Enzyme activity studies and structures on membranes show how these G proteins act by separate, independent mechanisms, leading to a product rule of co-stimulation when they act together. The findings explain how cells achieve robust stimulation of in the setting of very low background activity, properties essential to cell health and survival.