Phospholipase C-beta 1 is a GTPase-activating protein for Gq/11, its physiologic regulator

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

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

Phospholipase C-beta 1 is a GTPase-activating protein for Gq/11, its physiologic regulator

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

University of Texas, Southwestern Medical Center
Vanderbilt University School of Medicine
Lung and Blood Institute National Institutes of Health
Yonsei University College of Medicine

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

Abstract

Purified M1 muscarinic cholinergic receptor and Gq/11 were coreconstituted in lipid vesicles. Addition of purified phospholipase C-beta 1 (PLC-beta 1) 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-beta 1 caused a rapid burst of hydrolysis of Gq/11-bound GTP that was at least 50-fold faster than in its absence. Thus, PLC-beta 1 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-beta 1 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.

Original language	English
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
Publication status	Published - 7 Aug 1992
Externally published	Yes

Keywords

Animals
Atropine/pharmacology
Catechols/pharmacology
Enzyme Activation
GTP Phosphohydrolases/metabolism
GTP-Binding Proteins/metabolism
GTPase-Activating Proteins
Guanosine Diphosphate/metabolism
Guanosine Triphosphate/metabolism
Humans
Hydrolysis
Kinetics
Proteins/metabolism
Receptors, Adrenergic, beta/metabolism
Receptors, Muscarinic/metabolism
Turkeys
Type C Phospholipases/metabolism

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10.1016/0092-8674(92)90165-9

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title = "Phospholipase C-beta 1 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-beta 1 (PLC-beta 1) 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-beta 1 caused a rapid burst of hydrolysis of Gq/11-bound GTP that was at least 50-fold faster than in its absence. Thus, PLC-beta 1 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-beta 1 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.",

keywords = "Animals, Atropine/pharmacology, Catechols/pharmacology, Enzyme Activation, GTP Phosphohydrolases/metabolism, GTP-Binding Proteins/metabolism, GTPase-Activating Proteins, Guanosine Diphosphate/metabolism, Guanosine Triphosphate/metabolism, Humans, Hydrolysis, Kinetics, Proteins/metabolism, Receptors, Adrenergic, beta/metabolism, Receptors, Muscarinic/metabolism, Turkeys, Type C Phospholipases/metabolism",

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

year = "1992",

month = aug,

day = "7",

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

language = "English",

volume = "70",

pages = "411--418",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier BV",

number = "3",

}

TY - JOUR

T1 - Phospholipase C-beta 1 is a GTPase-activating protein for Gq/11, its physiologic regulator

AU - Berstein, Gabriel

AU - Blank, Jonathan

AU - Jhon, Deok-Young

AU - Exton, John H.

AU - Rhee, Sue Goo

AU - Ross, Elliott M.

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-beta 1 (PLC-beta 1) 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-beta 1 caused a rapid burst of hydrolysis of Gq/11-bound GTP that was at least 50-fold faster than in its absence. Thus, PLC-beta 1 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-beta 1 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-beta 1 (PLC-beta 1) 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-beta 1 caused a rapid burst of hydrolysis of Gq/11-bound GTP that was at least 50-fold faster than in its absence. Thus, PLC-beta 1 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-beta 1 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.

KW - Animals

KW - Atropine/pharmacology

KW - Catechols/pharmacology

KW - Enzyme Activation

KW - GTP Phosphohydrolases/metabolism

KW - GTP-Binding Proteins/metabolism

KW - GTPase-Activating Proteins

KW - Guanosine Diphosphate/metabolism

KW - Guanosine Triphosphate/metabolism

KW - Humans

KW - Hydrolysis

KW - Kinetics

KW - Proteins/metabolism

KW - Receptors, Adrenergic, beta/metabolism

KW - Receptors, Muscarinic/metabolism

KW - Turkeys

KW - Type C Phospholipases/metabolism

U2 - 10.1016/0092-8674(92)90165-9

DO - 10.1016/0092-8674(92)90165-9

M3 - Article

C2 - 1322796

SN - 0092-8674

VL - 70

SP - 411

EP - 418

JO - Cell

JF - Cell

IS - 3

ER -

Phospholipase C-beta 1 is a GTPase-activating protein for Gq/11, its physiologic regulator

Abstract

Keywords

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