Identification of T cell death-associated gene 8 ( TDAG8) as a novel acid sensing G-protein-coupled receptor
Identification of T cell death-associated gene 8 ( TDAG8) as a novel acid sensing G-protein-coupled receptor
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DOI：
10.1074/jbc.m407832200
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发表时间：
2005-03-11
影响因子：
4.8
通讯作者：
Shimizu, T
中科院分区：
文献类型：
--
作者：
Ishii, S;Kihara, Y;Shimizu, T
T细胞死亡相关基因8(TDAG8)是一种G蛋白偶联受体，主要在淋巴组织和肿瘤组织中表达。TDAG8与最近报道的质子敏感G蛋白偶联受体G2A、OGR1和GPR4有很高的氨基酸序列同源性。在这里，我们已经确定TDAG8是一个新的质子传感受体。在酸刺激下，稳定表达的TDAG8从细胞膜内化。作为TDAG8下游的一条信号通路，在pH值低于7.2的溶液中，可以观察到cAMP的积累。此外，酸刺激的TDAG8还可引起RhoA活化和肌动蛋白重排。这些结果提示，TDAG8在伴有组织酸中毒的条件下，可能在免疫反应和细胞转化中发挥生物学作用。
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.