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J. Biol. Chem., Vol. 280, Issue 10, 9083-9087, March 11, 2005

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Identification of T Cell Death-associated Gene 8 (TDAG8) as a Novel Acid Sensing G-protein-coupled Receptor^*

Satoshi Ishii, Yasuyuki Kihara, and Takao Shimizu

From the Department of Biochemistry and Molecular Biology, Faculty of Medicine, the University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

T cell death-associated gene 8 (TDAG8) is a G-protein-coupled receptor mainly expressed in lymphoid organs and cancer tissues. TDAG8 shares high amino acid sequence homologies with recently reported proton-sensing G-protein-coupled receptors, G2A, OGR1, and GPR4. Here we have identified TDAG8 as a novel proton-sensing receptor. Upon acid stimulation, stably expressed TDAG8 was internalized from the plasma membrane. As a signaling pathway downstream of TDAG8, accumulation of cyclic AMP was observed in response to solutions with a pH value lower than 7.2. Furthermore, RhoA activation and actin rearrangement were elicited by acid-stimulated TDAG8. These results suggest that TDAG8 may play biological roles in immune response and cellular transformation under conditions accompanying tissue acidosis.

Received for publication, July 12, 2004 , and in revised form, November 30, 2004.

^* This work was supported in part by grants-in-aid from the Ministry of Education, Science, Culture, Sports and Technology of Japan (to T. S. and S. I.) and a grant-in-aid for Comprehensive Research on Aging and Health from the Ministry of Health, Labor and Welfare, Japan (to S. I.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 81-3-5802-2925; Fax: 81-3-3813-3732; E-mail: mame{at}m.u-tokyo.ac.jp.

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