PT  - JOURNAL ARTICLE
AU  - Ai Ogawa
AU  - Hideru Obinata
AU  - Tomoyasu Hattori
AU  - Mikiko Kishi
AU  - Kazuaki Tatei
AU  - Osamu Ishikawa
AU  - Takashi Izumi
TI  - Identification and Analysis of Two Splice Variants of Human G2A Generated by Alternative Splicing
AID  - 10.1124/jpet.109.158758
DP  - 2010 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 469--478
VI  - 332
IP  - 2
4099  - http://jpet.aspetjournals.org/content/332/2/469.short
4100  - http://jpet.aspetjournals.org/content/332/2/469.full
SO  - J Pharmacol Exp Ther2010 Feb 01; 332
AB  - G2A is a G protein-coupled receptor that can be induced by various stressors. G2A is reported to have proton-sensing activity that mediates intracellular inositol phosphate (IP) accumulation with decreasing pH. We previously showed that G2A is also activated by some oxidized free fatty acids such as 9-hydroxyoctadecadienoic acid (9-HODE). In this study, we identified a novel alternative splice variant of G2A (G2A-b) that has a partially different N terminus compared with the G2A originally reported (G2A-a). The two splice variants of G2A show similar tissue distributions, but G2A-b is expressed more abundantly. There was no difference between the two variants in 9-HODE-induced cellular responses, such as intracellular calcium mobilization and GDP/GTP exchange of Gα protein, and in proton-sensitive IP accumulation. However, G2A-b showed a higher basal activity in terms of IP accumulation. Mutagenesis study revealed that the difference in the basal activity is attributable to the K7 residue that exists only in G2A-a. We further demonstrated that an R42A mutation largely impaired both the basal and proton-sensing activities, but did not affect the 9-HODE-induced intracellular calcium increase. Taken together, we found an additional novel G2A variant (G2A-b) that is the major transcript with functional response to ligand stimulation as well as G2A-a, and succeeded in discriminating proton-sensing and oxidized fatty acid-sensing activities of G2A. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics