Increased ubiquitination and the crosstalk of G protein signaling in cardiac myocytes: involvement of Ric‐8B in Gs suppression by Gq signal

• Published in: Genes to cells : devoted to molecular & cellular mechanisms Vol. 18; no. 12; pp. 1095 - 1106
• Main Authors: Jenie, Riris I, Nishimura, Motoki, Fujino, Mika, Nakaya, Michio, Mizuno, Norikazu, Tago, Kenji, Kurose, Hitoshi, Itoh, Hiroshi
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2013
• Subjects: Animals; Cardiomegaly - metabolism; Cardiomyocytes; Cells, Cultured; Cyclic AMP; Cyclic AMP - metabolism; GTP-Binding Protein alpha Subunits, Gq-G11 - genetics; GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism; GTP-Binding Protein alpha Subunits, Gs - metabolism; Guanine Nucleotide Exchange Factors - metabolism; HEK293 Cells; Humans; Male; Mice; Mice, Inbred C57BL; Myocytes, Cardiac - metabolism; NIH 3T3 Cells; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1 - metabolism; Receptors, Adrenergic, beta - metabolism; Rodents; Signal Transduction; Ubiquitination
• 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.