Ric-8B stabilizes the α subunit of stimulatory G protein by inhibiting its ubiquitination

Yusuke Nagai, Akiyuki Nishimura, Kenji Tago, Norikazu Mizuno, Hiroshi Itoh

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The α subunit of stimulatory G protein (Gα s ) activates adenylyl cyclase, which catalyzes cAMP production, and regulates many physiological aspects, such as cardiac regulation and endocrine systems. Ric-8B (resistance to inhibitors of cholinesterase 8B) has been identified as the Gα s -binding protein; however, its role in G s signaling remains obscure. In this study, we present evidence that Ric-8B specifically and positively regulates G s signaling by stabilizing the Gα s protein. An in vitro biochemical study suggested that Ric-8B does not possess guanine nucleotide exchange factor activity. However, knockdown of Ric-8B attenuated β-adrenergic agonist-induced cAMP accumulation, indicating that Ric-8B positively regulates G s signaling. Interestingly, overexpression and knockdown of Ric-8B resulted in an increase and a decrease in the Gα s protein, respectively, without affecting the Gα s mRNA level.We found that the Gα s protein is ubiquitinated and that this ubiquitination is inhibited by Ric-8B. This Ric-8B-mediated inhibition of Gα s ubiquitination requires interaction between Ric-8B and Gα s because Ric-8B splicing variants, which are defective for Gα s binding, failed to inhibit the ubiquitination. Taken together, these results suggest that Ric-8B plays a critical and specific role in the control of Gα s protein levels by modulating Gα s ubiquitination and positively regulates G s signaling.

Original languageEnglish
Pages (from-to)11114-11120
Number of pages7
JournalJournal of Biological Chemistry
Volume285
Issue number15
DOIs
Publication statusPublished - Apr 9 2010

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Ubiquitination
Cholinesterase Inhibitors
GTP-Binding Proteins
Proteins
Ubiquitinated Proteins
Guanine Nucleotide Exchange Factors
Adrenergic Agonists
Endocrine System
Adenylyl Cyclases
Carrier Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ric-8B stabilizes the α subunit of stimulatory G protein by inhibiting its ubiquitination. / Nagai, Yusuke; Nishimura, Akiyuki; Tago, Kenji; Mizuno, Norikazu; Itoh, Hiroshi.

In: Journal of Biological Chemistry, Vol. 285, No. 15, 09.04.2010, p. 11114-11120.

Research output: Contribution to journalArticle

Nagai, Yusuke ; Nishimura, Akiyuki ; Tago, Kenji ; Mizuno, Norikazu ; Itoh, Hiroshi. / Ric-8B stabilizes the α subunit of stimulatory G protein by inhibiting its ubiquitination. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 15. pp. 11114-11120.
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