Phospholipase C-β1 is a GTPase-activating protein for Gq/11, its physiologic regulator

Gabriel Berstein; Jonathan L. Blank; Deok Young Jhon; John H. Exton; Sue Goo Rhee; Elliott M. Ross

doi:10.1016/0092-8674(92)90165-9

Phospholipase C-β1 is a GTPase-activating protein for G_q/11, its physiologic regulator

Gabriel Berstein, Jonathan L. Blank, Deok Young Jhon, John H. Exton, Sue Goo Rhee, Elliott M. Ross

Research output: Contribution to journal › Article › peer-review

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Abstract

Purified M1 muscarinic cholinergic receptor and G_q/11 were coreconstituted in lipid vesicles. Addition of purified phospholipase C-β1 (PLC-β1) further stimulated the receptor-promoted steady-state GTPase activity of G_q/11 up to 20-fold. Stimulation depended upon receptor-mediated GTP-GDP exchange. Addition of PLC-β1 caused a rapid burst of hydrolysis of G_q/11-bound GTP that was at least 50-fold faster than in its absence. Thus, PLC-β1 stimulates hydrolysis of G_q/11-bound GTP and acts as a GTPase-activating protein (GAP) for its physiologic regulator, G_q/11. GTPase-stimulating activity was specific both for PLC-β1 and G_q/11. Such GAP activity by an effector coupled to a trimeric G protein can reconcile slow GTP hydrolysis by pure G proteins in vitro with fast physiologic deactivation of G protein-mediated signaling.

Original language	English (US)
Pages (from-to)	411-418
Number of pages	8
Journal	Cell
Volume	70
Issue number	3
DOIs	https://doi.org/10.1016/0092-8674(92)90165-9
State	Published - Aug 7 1992

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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title = "Phospholipase C-β1 is a GTPase-activating protein for Gq/11, its physiologic regulator",

abstract = "Purified M1 muscarinic cholinergic receptor and Gq/11 were coreconstituted in lipid vesicles. Addition of purified phospholipase C-β1 (PLC-β1) further stimulated the receptor-promoted steady-state GTPase activity of Gq/11 up to 20-fold. Stimulation depended upon receptor-mediated GTP-GDP exchange. Addition of PLC-β1 caused a rapid burst of hydrolysis of Gq/11-bound GTP that was at least 50-fold faster than in its absence. Thus, PLC-β1 stimulates hydrolysis of Gq/11-bound GTP and acts as a GTPase-activating protein (GAP) for its physiologic regulator, Gq/11. GTPase-stimulating activity was specific both for PLC-β1 and Gq/11. Such GAP activity by an effector coupled to a trimeric G protein can reconcile slow GTP hydrolysis by pure G proteins in vitro with fast physiologic deactivation of G protein-mediated signaling.",

author = "Gabriel Berstein and Blank, {Jonathan L.} and Jhon, {Deok Young} and Exton, {John H.} and Rhee, {Sue Goo} and Ross, {Elliott M.}",

note = "Funding Information: This work was supported by Fogarty International Postdoctoral Fellowship TWO4475 to G. B. and by research grants from the National Institutes of Health (GM30355) and the R. A. Welch Foundation (I-092) to E M. R. We appreciate the suggestions of Tsutomu Higashijima and the unfettered criticism of this manuscript by Melanie Cobb.",

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doi = "10.1016/0092-8674(92)90165-9",

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T1 - Phospholipase C-β1 is a GTPase-activating protein for Gq/11, its physiologic regulator

AU - Berstein, Gabriel

AU - Blank, Jonathan L.

AU - Jhon, Deok Young

AU - Exton, John H.

AU - Rhee, Sue Goo

AU - Ross, Elliott M.

N1 - Funding Information: This work was supported by Fogarty International Postdoctoral Fellowship TWO4475 to G. B. and by research grants from the National Institutes of Health (GM30355) and the R. A. Welch Foundation (I-092) to E M. R. We appreciate the suggestions of Tsutomu Higashijima and the unfettered criticism of this manuscript by Melanie Cobb.

PY - 1992/8/7

Y1 - 1992/8/7

N2 - Purified M1 muscarinic cholinergic receptor and Gq/11 were coreconstituted in lipid vesicles. Addition of purified phospholipase C-β1 (PLC-β1) further stimulated the receptor-promoted steady-state GTPase activity of Gq/11 up to 20-fold. Stimulation depended upon receptor-mediated GTP-GDP exchange. Addition of PLC-β1 caused a rapid burst of hydrolysis of Gq/11-bound GTP that was at least 50-fold faster than in its absence. Thus, PLC-β1 stimulates hydrolysis of Gq/11-bound GTP and acts as a GTPase-activating protein (GAP) for its physiologic regulator, Gq/11. GTPase-stimulating activity was specific both for PLC-β1 and Gq/11. Such GAP activity by an effector coupled to a trimeric G protein can reconcile slow GTP hydrolysis by pure G proteins in vitro with fast physiologic deactivation of G protein-mediated signaling.

AB - Purified M1 muscarinic cholinergic receptor and Gq/11 were coreconstituted in lipid vesicles. Addition of purified phospholipase C-β1 (PLC-β1) further stimulated the receptor-promoted steady-state GTPase activity of Gq/11 up to 20-fold. Stimulation depended upon receptor-mediated GTP-GDP exchange. Addition of PLC-β1 caused a rapid burst of hydrolysis of Gq/11-bound GTP that was at least 50-fold faster than in its absence. Thus, PLC-β1 stimulates hydrolysis of Gq/11-bound GTP and acts as a GTPase-activating protein (GAP) for its physiologic regulator, Gq/11. GTPase-stimulating activity was specific both for PLC-β1 and Gq/11. Such GAP activity by an effector coupled to a trimeric G protein can reconcile slow GTP hydrolysis by pure G proteins in vitro with fast physiologic deactivation of G protein-mediated signaling.

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Phospholipase C-β1 is a GTPase-activating protein for G_q/11, its physiologic regulator

Abstract

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