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Status: Bibliographieeintrag

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Verfasst von:Hippe, Hans-Jörg [VerfasserIn]   i
 Luedde, Mark [VerfasserIn]   i
 Lutz, Susanne [VerfasserIn]   i
 Koehler, Henrike [VerfasserIn]   i
 Eschenhagen, Thomas [VerfasserIn]   i
 Frey, Norbert [VerfasserIn]   i
 Katus, Hugo [VerfasserIn]   i
 Wieland, Thomas [VerfasserIn]   i
 Niroomand, Feraydoon [VerfasserIn]   i
Titel:Regulation of cardiac cAMP synthesis and contractility by nucleoside diphosphate kinase B/G protein βγ dimer complexes
Verf.angabe:Hans-Joerg Hippe, Mark Luedde, Susanne Lutz, Henrike Koehler, Thomas Eschenhagen, Norbert Frey, Hugo A. Katus, Thomas Wieland, and Feraydoon Niroomand
E-Jahr:2007
Jahr:15 March 2007
Umfang:9 S.
Fussnoten:Gesehen am 24.03.2022
Titel Quelle:Enthalten in: Circulation research
Ort Quelle:New York, NY : Assoc., 1953
Jahr Quelle:2007
Band/Heft Quelle:100(2007), 8, Seite 1191-1199
ISSN Quelle:1524-4571
Abstract:Heterotrimeric G proteins are pivotal regulators of myocardial contractility. In addition to the receptor-induced GDP/GTP exchange, G protein α subunits can be activated by a phosphate transfer via a plasma membrane-associated complex of nucleoside diphosphate kinase B (NDPK B) and G protein βγ-dimers (Gβγ). To investigate the physiological role of this phosphate transfer in cardiomyocytes, we generated a Gβ1γ2-dimer carrying a single amino acid exchange at the intermediately phosphorylated His-266 in the β1 subunit (Gβ1H266Lγ2). Recombinantly expressed Gβ1H266Lγ2 were integrated into heterotrimeric G proteins in rat cardiomyocytes but were deficient in intermediate Gβ phosphorylation. Compared with wild-type Gβ1γ2 (Gβ1WTγ2), overexpression of Gβ1H266Lγ2 suppressed basal cAMP formation up to 55%. A similar decrease in basal cAMP production occurred when the formation of NDPK B/Gβγ complexes was attenuated by siRNA-mediated NDPK B knockdown. In adult rat cardiomyocytes expressing Gβ1H266Lγ2, the basal contractility was suppressed by ≈50% which correlated to similarly reduced basal cAMP levels and reduced Ser16-phosphorylation of phospholamban. In the presence of the β-adrenoceptor agonist isoproterenol, the total cAMP formation and contractility were significantly lower in Gβ1H266Lγ2 than in Gβ1WTγ2 expressing cardiomyocytes. However, the relative isoproterenol-induced increased was not affected by Gβ1H266Lγ2. We conclude that the receptor-independent activation of G proteins via NDPK B/Gβγ complexes requires the intermediate phosphorylation of G protein β subunits at His-266. Our results highlight the histidine kinase activity of NDPK B for Gβ and demonstrate its contribution to the receptor-independent regulation of cAMP synthesis and contractility in intact cardiomyocytes.
DOI:doi:10.1161/01.RES.0000264058.28808.cc
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1161/01.RES.0000264058.28808.cc
 Volltext: https://www.ahajournals.org/doi/10.1161/01.RES.0000264058.28808.cc
 DOI: https://doi.org/10.1161/01.RES.0000264058.28808.cc
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:cAMP
 cardiomyocytes
 contractility
 G proteins
 NDPK
K10plus-PPN:1796561533
Verknüpfungen:→ Zeitschrift

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