| Online-Ressource |
Verfasst von: | Hippe, Hans-Jörg [VerfasserIn]  |
| Luedde, Mark [VerfasserIn]  |
| Lutz, Susanne [VerfasserIn]  |
| Koehler, Henrike [VerfasserIn]  |
| Eschenhagen, Thomas [VerfasserIn]  |
| Frey, Norbert [VerfasserIn]  |
| Katus, Hugo [VerfasserIn]  |
| Wieland, Thomas [VerfasserIn]  |
| Niroomand, Feraydoon [VerfasserIn]  |
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 |
Regulation of cardiac cAMP synthesis and contractility by nucleoside diphosphate kinase B/G protein βγ dimer complexes / Hippe, Hans-Jörg [VerfasserIn]; 15 March 2007 (Online-Ressource)