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

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.
Mesh Terms:
Animals, Baculoviridae, Brain, Calcium, Cell Membrane, Cells, Cultured, Cytosol, Endothelin-1, Extracellular Signal-Regulated MAP Kinases, GTP-Binding Protein alpha Subunits, Gq-G11, Gene Silencing, Guanine, Guanine Nucleotide Exchange Factors, Humans, Mice, Microscopy, Fluorescence, Nuclear Proteins, Peptides, Cyclic, Protein Transport, RNA, Small Interfering, Rats, Receptors, G-Protein-Coupled, Signal Transduction, Time Factors, Two-Hybrid System Techniques
Genes Cells
Date: May. 01, 2006
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