Identification of T cell death-associated gene 8 (TDAG8) as a novel acid sensing G-protein-coupled receptor.
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.
Ishii
Satoshi
S
Department of Biochemistry and Molecular Biology, Faculty of Medicine, the University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. mame@m.u-tokyo.ac.jp
Kihara
Yasuyuki
Y
Shimizu
Takao
T
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016466:CHO Cells; D016923:Cell Death; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007109:Immunity; D016366:Open Reading Frames; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*; D014162:Transfection
C513334:GPR65 protein, human; D043562:Receptors, G-Protein-Coupled; D000242:Cyclic AMP