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Verfasst von:Vettel, Christiane [VerfasserIn]   i
 Wittig, Karola [VerfasserIn]   i
 Vogt, Andreas [VerfasserIn]   i
 Wieland, Thomas [VerfasserIn]   i
Titel:A novel player in cellular hypertrophy
Titelzusatz:Giβγ/PI3K-dependent activation of the RacGEF TIAM-1 is required for α1-adrenoceptor induced hypertrophy in neonatal rat cardiomyocytes
Verf.angabe:Christiane Vettel, Karola Wittig, Andreas Vogt, Christina M. Wuertz, Ali El-Armouche, Susanne Lutz, Thomas Wieland
E-Jahr:2012
Jahr:August 2012
Umfang:11 S.
Illustrationen:Illustrationen
Fussnoten:Das i in Giβγ/PI3K-dependent ist tiefgestellt ; Available online 4 May 2012 ; Gesehen am 12.10.2018
Titel Quelle:Enthalten in: Journal of molecular and cellular cardiology
Ort Quelle:New York, NY [u.a.] : Elsevier, 1970
Jahr Quelle:2012
Band/Heft Quelle:53(2012), 2, Seite 165-175
ISSN Quelle:1095-8584
Abstract:Activation of α1-adrenoceptors (α1-AR) by high catecholamine levels, e.g. in heart failure, is thought to be a driving force of cardiac hypertrophy. In this context several downstream mediators and cascades have been identified to potentially play a role in cardiomyocyte hypertrophy. One of these proteins is the monomeric G protein Rac1. However, until now it is unclear how this essential G protein is activated by α1-AR agonists and what are the downstream targets inducing cellular growth. By using protein-based as well as pharmacological inhibitors and the shRNA technique, we demonstrate that in neonatal rat cardiomyocytes (NRCM) Rac1 is activated via a cascade involving the α1A-AR subtype, Giβγ, the phosphoinositide-3′-kinase and the guanine nucleotide exchange factor Tiam1. We further demonstrate that this signaling induces an increase in protein synthesis, cell size and atrial natriuretic peptide expression. We identified the p21-activated kinase 2 (PAK2) as a downstream effector of Rac1 and were able to link this cascade to the activation of the pro-hypertrophic kinases ERK1/2 and p90RSK. Our data thus reveal a prominent role of the α1A-AR/Giβγ/Tiam1-mediated activation of Rac1 and its effector PAK2 in the induction of hypertrophy in NRCM.
DOI:doi:10.1016/j.yjmcc.2012.04.015
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: http://dx.doi.org/10.1016/j.yjmcc.2012.04.015
 Volltext: http://www.sciencedirect.com/science/article/pii/S0022282812001769
 DOI: https://doi.org/10.1016/j.yjmcc.2012.04.015
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Cellular hypertrophy
 Exchange factor
 Gi protein
 Guanine nucleotide
 Neonatal rat cardiomyocytes
 p21 activated kinase
 Rac1
 RhoGTPases
 Tiam1
 α1-Adrenoceptor
K10plus-PPN:1581852355
Verknüpfungen:→ Zeitschrift

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