Abstract
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.
Highlights
Three GPCRs, i.e. ovarian cancer G-protein-coupled receptor 1 (OGR1, known as GPR68) [6], GPR4 [7, 8], and G2A [9]
We show that T cell death-associated gene 8 (TDAG8), heterologously expressed in mammalian cells, is a proton-sensing GPCR that stimulates cAMP formation, activates Rho, and induces stress fiber formation
PH-dependent Activation of cAMP Formation by TDAG8 —To test whether TDAG8, which shares high homologies with G2A, OGR1, and GPR4, is a proton sensor, CHO-S cells were stably transfected with the expression vector for TDAG8
Summary
Three GPCRs, i.e. ovarian cancer G-protein-coupled receptor 1 (OGR1, known as GPR68) [6], GPR4 [7, 8], and G2A [9]. TDAG8 shares high amino acid sequence homologies with recently reported proton-sensing G-protein-coupled receptors, G2A, OGR1, and GPR4. We show that TDAG8, heterologously expressed in mammalian cells, is a proton-sensing GPCR that stimulates cAMP formation, activates Rho, and induces stress fiber formation.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
