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Regulation of G protein function: Implications for heart disease

  • Johanna T. A. Meij
Chapter
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 17)

Abstract

Heterotrimeric GTP-binding and -hydrolyzing proteins (G proteins) link members of a family of seven-helix transmembrane receptors (G protein-coupled receptors, GPCR) to intracellular effectors. The coupling mechanism involves the G protein completing a cycle of activation, dissociation into a and βγ subunits, deactivation, and reassociation. At the center of this cycle is the α subunit, in which activation by GPCR, GTPase activity, and regulation of effector are combined. Whereas Gα’s functional domains and residues had already been inferred from mutagenesis studies, the recent solution of the crystal structure has elucidated the structural basis of α subunit function. It is now clear that an irregularity in any GPCR pathway component could cause a physiological defect. This is confirmed by the identification of mutations in GPCR and Gα’s in various human diseases. Although several cardiomyopathies are associated with abnormal GPCR function, mutations are unlikely in these disorders. The last few years, other aspects of G protein function have moved into focus: e.g. posttranslational modifications; effector regulation by βγ subunits; GTPase activating protein (GAP) activity of effectors; G protein expression levels etc. When comparing the regulation of G protein functional activity in cAMP and in inositol phosphate generating pathways, an extrapolation can be made to data on the status of these pathways in some cardiovascular diseases.

Key words

G protein adenylate cyclase phospholipase C GAP heart disease 

Abbreviations

AC

adenylate cyclase

GPCR

G protein-coupled receptor

PLC

phospholipase C

GAP

GTPase activating protein

PTX

pertussis toxin

Ptdins(4,5)P2

phosphatidylinositol 4,5-bisphosphate

Ins(1,4,5)P3

inositol 1,4,5trisphosphate

CCh

carbachol

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Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Johanna T. A. Meij
    • 1
  1. 1.Department of PharmacologyUniversity of Texas Southwestern Medical CenterDallasUSA

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