9iv6

Structural highlights

Function

GPR4_HUMAN Proton-sensing G-protein coupled receptor couples to multiple intracellular signaling pathways, including GNAS/cAMP, GNAQ/phospholipase C (PLC), and GNA12/GNA13/Rho pathways (PubMed:12955148, PubMed:17462861, PubMed:20211729, PubMed:22110680). Acidosis-induced GPR4 activation increases paracellular gap formation and permeability of vascular endothelial cells through the GNA12/GNA13/Rho GTPase signaling pathway (PubMed:32058960). In the brain may mediate central respiratory sensitivity to CO(2)H(+) (By similarity).[UniProtKB:Q8BUD0]^{[1] [2] [3] [4] [5]}

References

1. ↑ Ludwig MG, Vanek M, Guerini D, Gasser JA, Jones CE, Junker U, Hofstetter H, Wolf RM, Seuwen K. Proton-sensing G-protein-coupled receptors. Nature. 2003 Sep 4;425(6953):93-8. PMID:12955148 doi:10.1038/nature01905
2. ↑ Tobo M, Tomura H, Mogi C, Wang JQ, Liu JP, Komachi M, Damirin A, Kimura T, Murata N, Kurose H, Sato K, Okajima F. Previously postulated "ligand-independent" signaling of GPR4 is mediated through proton-sensing mechanisms. Cell Signal. 2007 Aug;19(8):1745-53. PMID:17462861 doi:10.1016/j.cellsig.2007.03.009
3. ↑ Liu JP, Nakakura T, Tomura H, Tobo M, Mogi C, Wang JQ, He XD, Takano M, Damirin A, Komachi M, Sato K, Okajima F. 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. Pharmacol Res. 2010 Jun;61(6):499-505. PMID:20211729 doi:10.1016/j.phrs.2010.02.013
4. ↑ Chen A, Dong L, Leffler NR, Asch AS, Witte ON, Yang LV. Activation of GPR4 by acidosis increases endothelial cell adhesion through the cAMP/Epac pathway. PLoS One. 2011;6(11):e27586. PMID:22110680 doi:10.1371/journal.pone.0027586
5. ↑ Krewson EA, Sanderlin EJ, Marie MA, Akhtar SN, Velcicky J, Loetscher P, Yang LV. The Proton-Sensing GPR4 Receptor Regulates Paracellular Gap Formation and Permeability of Vascular Endothelial Cells. iScience. 2020 Feb 21;23(2):100848. PMID:32058960 doi:10.1016/j.isci.2020.100848