Ric-8A potentiates Gq-mediated signal transduction by acting downstream of G protein-coupled receptor in intact cells

Akiyuki Nishimura, Miyuki Okamoto, Yo Sugawara, Norikazu Mizuno, Junji Yamauchi, Hiroshi Itoh

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

RIC-8 was originally found by genetic studies on in vitro as a guanine nucleotide exchange factor for G protein α subunits. However, the physiological role of a mammalian homolog Ric-8A on G protein-coupled receptor signaling in intact cells is largely unknown. We isolated Ric-8A using a yeast two-hybrid system with Gαq and examined the role of Ric-8A on Gq-mediated signaling. The small interfering RNA of Ric-8A diminished the Gq-coupled receptor-mediated ERK activation and intracellular calcium mobilization in 293T cells. Ric-8A was translocated to the cell membrane in response to the Gq-coupled receptor stimulation. The expression of the myristoylation sequence-conjugated Ric-8A mutant was located in the membranes and shown to enhance the Gq-coupled receptor-mediated ERK activation. Moreover, this enhancement on ERK activation and the guanine nucleotide exchange activity of Ric-8A for Gαq were inhibited by Gq selective inhibitor YM-254890. These results suggested that Ric-8A potentiates Gq-mediated signal transduction by acting as a novel-type regulator in intact cells.

Original languageEnglish
Pages (from-to)487-498
Number of pages12
JournalGenes to Cells
Volume11
Issue number5
DOIs
Publication statusPublished - May 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

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