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Ric‐8A potentiates Gq‐mediated signal transduction by acting downstream of G protein‐coupled receptor in intact cells
Author(s) -
Nishimura Akiyuki,
Okamoto Miyuki,
Sugawara Yo,
Mizuno Norikazu,
Yamauchi Junji,
Itoh Hiroshi
Publication year - 2006
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2006.00959.x
Subject(s) - gq alpha subunit , biology , g protein , signal transduction , microbiology and biotechnology , guanine nucleotide exchange factor , mapk/erk pathway , hek 293 cells , g protein coupled receptor , receptor , gtp binding protein regulators , myristoylation , biochemistry , phosphorylation
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 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.