Increased ubiquitination and the crosstalk of G protein signaling in cardiac myocytes: involvement of R ic‐8 B in G s suppression by G q signal

• Published in: Genes to cells : devoted to molecular & cellular mechanisms 2013-12, Vol.18 (12), p.1095-1106
• Main Authors: Jenie, Riris I, Nishimura, Motoki, Fujino, Mika, Nakaya, Michio, Mizuno, Norikazu, Tago, Kenji, Kurose, Hitoshi, Itoh, Hiroshi
• Format: Article
• Language: English
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/gtc.12099

Hyperactivation of Gq signaling causes cardiac hypertrophy, and β‐adrenergic receptor‐mediated Gs signaling is attenuated in hypertrophic cardiomyocytes. Here, we found the increase in a global ubiquitination in hypertrophic mouse heart. The activation of Gq signaling resulted in the ubiquitination of Gαs in neonatal rat cardiomyocytes, reduced Gαs expression, and suppressed cAMP response to β‐adrenergic receptor stimulation. Ectopic expression of Gαq induced a similar suppression, which is due to the degradation of Gαs by a ubiquitin–proteasome pathway. Co‐expression of Ric‐8B, a positive regulator of Gαs, effectively canceled the Gαq‐induced ubiquitination of Gαs and recovered the cAMP accumulation. In vitro , Gαq competes for the binding of Gαs to Ric‐8B. These data show a new role of Ric‐8B in the crosstalk of two distinct G protein signaling pathways, which are possibly involved in a part of mechanisms of chronic heart failure.