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

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
Akiyuki NishimuraHiroshi Itoh

Abstract

RIC-8 was originally found by genetic studies on C. elegans mutants that were resistant to inhibitors of acetylcholinesterase and reported to act in vitro as a guanine nucleotide exchange factor for G protein alpha 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 Galphaq 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 Galphaq 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.

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Citations

Feb 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Mikel Garcia-MarcosMarilyn G Farquhar
Jul 20, 2010·Proceedings of the National Academy of Sciences of the United States of America·Akiyuki NishimuraHiroshi Itoh
Feb 17, 2010·The Journal of Biological Chemistry·Mikel Garcia-MarcosMarilyn G Farquhar
Feb 6, 2010·The Journal of Biological Chemistry·Yusuke NagaiHiroshi Itoh
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Oct 19, 2013·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Riris I JenieHiroshi Itoh
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