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The proton-sensing G-protein coupled receptor GPR4 promotes angiogenesis in head and neck cancer.
433 hypermethylated genes were discovered such as Gpr4, Dgcr8, Zeb2, Dixdc1, Sox2, Shh, Lrfn3, Det1, Shox2, Abracl, Trdn, Irx2, Pabpc6, Sbk1, and Peg3.134 hypomethylated genes which included Gpr126, Birc2, Sepw1, Irgq, Atp5sl, Hipk4, Ttc9b, Tulp2, Bex1, Mex3b, Ctsc, Gucy2d, Rrm1, Fam160a2, and Cdkn1c were revealed.
Recent studies suggest that OGR1-family GPCRs, including OGR1 (GPR68), GPR4, and T cell-death associated gene 8 (TDAG8 or GPR65), also sense extracellular protons and, thereby, stimulates a variety of cellular activities through several types of G proteins [18-21] (Figure 1).
GPR4 has been shown to be expressed in endothelial cells and to be activated by extracellular acidification, leading to accumulation of cAMP, which may be relevant to normal blood vessel formation .
Mogi et al., "Previously postulated "ligand-independent" signaling of GPR4 is mediated through proton-sensing mechanisms," Cellular Signalling, vol.
Tomura et al., "Each one of certain histidine residues in G-protein-coupled receptor GPR4 is critical for extracellular proton-induced stimulation of multiple G-protein-signaling pathways," Pharmacological Research, vol.
Roy et al., "Vascular abnormalities in mice deficient for the G protein-coupled receptor GPR4 that functions as a pH sensor," Molecular and Cellular Biology, vol.
(28) Los LPC actuan por medio de dos receptores membranales: GPR4, GPR8 y GPR132.
Recently, two G-protein-coupled receptors with a high affinity for LPC were identified: G2A, which is an immunoregulatory receptor (7), and GPR4, which is a receptor for LPC and sphingosylphosphorylcholine (8).
In summary, LPC has been shown to function as a signaling molecule that binds to the G-protein-coupled receptors G2A (7) and GPR4 (8).
Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4. J Biol Chem 2001;276:41325-35.
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