caa a22 4500 477120105 CHVBK 20180405111634.0 cr unu---uuuuu 170330e19960401xx s 000 0 eng 10.1007/BF00227878 doi (NATIONALLICENCE)springer-10.1007/BF00227878 Meij Johanna Department of Pharmacology, University of Texas Southwestern Medical Center, 75235-9041, Dallas, TX, USA aut Regulation of G protein function: Implications for heart disease [Elektronische Daten] [Johanna Meij] 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 α 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. Kluwer Academic Publishers, 1996 G protein nationallicence adenylate cyclase nationallicence phospholipase C nationallicence GAP nationallicence heart disease nationallicence signal transduction nationallicence AC : adenylate cyclase nationallicence GPCR : G protein-coupled receptor nationallicence PLC : phospholipase C nationallicence GAP : GTPase activating protein nationallicence PTX : pertussis toxin nationallicence Ptdins(4,5) P 2 : phosphatidylinositol 4,5-bisphosphate nationallicence Ins(1,4,5) P 3 : inositol 1,4,5-trisphosphate nationallicence CCh : carbachol nationallicence Molecular and Cellular Biochemistry Kluwer Academic Publishers 157/1-2(1996-04-01), 31-38 0300-8177 157:1-2<31 1996 157 11010 https://doi.org/10.1007/BF00227878 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00227878 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Meij Johanna Department of Pharmacology, University of Texas Southwestern Medical Center, 75235-9041, Dallas, TX, USA aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Kluwer Academic Publishers 157/1-2(1996-04-01), 31-38 0300-8177 157:1-2<31 1996 157 11010 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer