Dissociation of the G protein βγ from the Gq–PLCβ complex partially attenuates PIP2 hydrolysis

Abstract

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Molecular regulation of GPCR-G-protein-governed PIP3 generation and its adaptation

“…Though GαqGTP is the highly efficient PLCβ activator, Gβγ also stimulates PLCβ and induces PIP2 hydrolysis 33 . We have shown that PIP2 hydrolysis induced by Gβγ alone is modest compared to the robust hydrolysis induced by GαqGTP 34 . Since α2AR is a Gi/o-GPCR, upon activation, Gβγ should be the only available PLCβ activator.…”

“…DNA constructs used were as follows; DNA constructs used for Blue opsin-mTurquoise, mCherry-Gγ3-CC mutant, fluorescently tagged Akt-PH, CRY2-mCherry-RGS4Δ, and PH, Lyn-HTH have been described previously 34,45,52,56,57 . CIBN-CAAX was cloned into the pcDNA3.1 vector in our lab.…”

Capsaicin inhibits intestinal Cl- secretion and promotes Na+ absorption by blocking TRPV4 channels in healthy and colitic mice

“…We initially applied RN1747, GSK1016790A, and 4α-PPD, three selective TRPV4 activators with different chemical structures, but all of them did not alter basal colonic I sc in WT mice (data not shown, n = 6). Since TRPV4 channels could be suppressed by phosphatidylinositol 4,5-bisphosphate (PIP 2 ) under the resting state ( 28 ), we tested if this also happens in the intestine by hydrolyzing PIP 2 via activation of phospholipase C (PLC) and phospholipase A2 (PLA 2 ) during cholinergic signaling ( 29 , 30 , 31 ). The active PLC inhibitor U73122 (30 μM), but not its inactive form U73343 (10 μM), attenuated TRPV4 activator RN1747-potentiated I sc induced by CCh (50 μM) ( Fig.…”

Cancer-Associated Mutations Enhance The Sensitivity Of The Trupath GαQ/11 System

“…On top of this, it has long been known that measurement of GTPase activity of native Gα q is challenging, as it occurs more rapidly compared to other Gα subunits, especially under physiological conditions (Mizuno & Itoh, 2009; Mukhopadhyay & Ross, 1999). The intrinsic GTPase activity of Gα q is enhanced by expression of GTPase activating proteins (GAPs), namely PLC-β, RGS4 and GAIP (Anger, Zhang, & Mende, 2004; Hepler, Berman, Gilman, & Kozasa, 1997; Kankanamge et al, 2021). The high rate of intrinsic GTPase activity coupled with endogenous expression of GAPs in HEK293T cells suggests that the kinetics of inactivation of G q/11 may be very high.…”