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Gene Review

GPR4  -  G protein-coupled receptor 4

Homo sapiens

Synonyms: G-protein coupled receptor 19, G-protein coupled receptor 4, GPR19
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Disease relevance of GPR4


High impact information on GPR4

  • The analysis of intracellular cAMP levels showed that gpr4 mutants still respond to glucose but not to certain amino acids, such as methionine [4].
  • Unexpectedly, the acid-induced cAMP accumulation was also largely inhibited by OGR1 siRNA but only slightly by GPR4 siRNA [5].
  • SPC and LPC stimulate DNA synthesis in GPR4-expressing Swiss 3T3 cells [6].
  • SPC and LPC bind to GPR4 in GPR4-transfected CHO cells with K(d)/SPC = 36 nm, and K(d)/LPC = 159 nm, respectively [6].
  • Both SPC and LPC activate GPR4-dependent activation of serum response element reporter and receptor internalization [6].

Biological context of GPR4


Anatomical context of GPR4

  • Here we show that GPR4 also malignantly transforms NIH3T3 cells and that TDAG8 malignantly transforms the normal mammary epithelial cell line NMuMG [7].
  • However, in a functional assay to examine the specificity of ligand binding, we found that neither SPC nor LPC, or other related lysophospholipids, induced internalization of GPR4 from the plasma membrane [10].
  • In addition, neither SPC nor LPC stimulated the binding of GTPgammaS to membranes prepared from GPR4 expressing cells and did not activate ERK1/2 [10].
  • Overall, we report that endothelial cells selectively expressed GPR4, a specific LPC receptor [11].
  • We developed a peptide Ab against GPR4 that detected GPR4 expression in transfected COS 7 cells and endogenous GPR4 expression in endothelial cells by Western blot [2].

Associations of GPR4 with chemical compounds


Other interactions of GPR4


Analytical, diagnostic and therapeutic context of GPR4

  • Northern blot analysis showed that GPR4 is widely expressed, with higher levels in kidney, heart, and especially lung, where it is at least fivefold greater than in other tissues [1].


  1. Isolation of a novel G protein-coupled receptor (GPR4) localized to chromosome 19q13.3. Mahadevan, M.S., Baird, S., Bailly, J.E., Shutler, G.G., Sabourin, L.A., Tsilfidis, C., Neville, C.E., Narang, M., Korneluk, R.G. Genomics (1995) [Pubmed]
  2. Lysophosphatidylcholine impairs endothelial barrier function through the G protein-coupled receptor GPR4. Qiao, J., Huang, F., Naikawadi, R.P., Kim, K.S., Said, T., Lum, H. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  3. Leucine-rich repeat-containing, G protein-coupled receptor 4 null mice exhibit intrauterine growth retardation associated with embryonic and perinatal lethality. Mazerbourg, S., Bouley, D.M., Sudo, S., Klein, C.A., Zhang, J.V., Kawamura, K., Goodrich, L.V., Rayburn, H., Tessier-Lavigne, M., Hsueh, A.J. Mol. Endocrinol. (2004) [Pubmed]
  4. G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA pathway in Cryptococcus neoformans. Xue, C., Bahn, Y.S., Cox, G.M., Heitman, J. Mol. Biol. Cell (2006) [Pubmed]
  5. Prostaglandin I(2) production and cAMP accumulation in response to acidic extracellular pH through OGR1 in human aortic smooth muscle cells. Tomura, H., Wang, J.Q., Komachi, M., Damirin, A., Mogi, C., Tobo, M., Kon, J., Misawa, N., Sato, K., Okajima, F. J. Biol. Chem. (2005) [Pubmed]
  6. Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4. Zhu, K., Baudhuin, L.M., Hong, G., Williams, F.S., Cristina, K.L., Kabarowski, J.H., Witte, O.N., Xu, Y. J. Biol. Chem. (2001) [Pubmed]
  7. G protein-coupled receptors GPR4 and TDAG8 are oncogenic and overexpressed in human cancers. Sin, W.C., Zhang, Y., Zhong, W., Adhikarakunnathu, S., Powers, S., Hoey, T., An, S., Yang, J. Oncogene (2004) [Pubmed]
  8. Isolation of three novel human genes encoding G protein-coupled receptors. Heiber, M., Docherty, J.M., Shah, G., Nguyen, T., Cheng, R., Heng, H.H., Marchese, A., Tsui, L.C., Shi, X., George, S.R. DNA Cell Biol. (1995) [Pubmed]
  9. Cloning, sequencing and tissue distribution of two related G protein-coupled receptor candidates expressed prominently in human lung tissue. An, S., Tsai, C., Goetzl, E.J. FEBS Lett. (1995) [Pubmed]
  10. The G protein-coupled receptor GPR4 suppresses ERK activation in a ligand-independent manner. Bektas, M., Barak, L.S., Jolly, P.S., Liu, H., Lynch, K.R., Lacana, E., Suhr, K.B., Milstien, S., Spiegel, S. Biochemistry (2003) [Pubmed]
  11. Inflammatory stress increases receptor for lysophosphatidylcholine in human microvascular endothelial cells. Lum, H., Qiao, J., Walter, R.J., Huang, F., Subbaiah, P.V., Kim, K.S., Holian, O. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  12. TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor. Wang, J.Q., Kon, J., Mogi, C., Tobo, M., Damirin, A., Sato, K., Komachi, M., Malchinkhuu, E., Murata, N., Kimura, T., Kuwabara, A., Wakamatsu, K., Koizumi, H., Uede, T., Tsujimoto, G., Kurose, H., Sato, T., Harada, A., Misawa, N., Tomura, H., Okajima, F. J. Biol. Chem. (2004) [Pubmed]
  13. Proton-sensing G-protein-coupled receptors. Ludwig, M.G., Vanek, M., Guerini, D., Gasser, J.A., Jones, C.E., Junker, U., Hofstetter, H., Wolf, R.M., Seuwen, K. Nature (2003) [Pubmed]
  14. GPR4 plays a critical role in endothelial cell function and mediates the effects of sphingosylphosphorylcholine. Kim, K.S., Ren, J., Jiang, Y., Ebrahem, Q., Tipps, R., Cristina, K., Xiao, Y.J., Qiao, J., Taylor, K.L., Lum, H., Anand-Apte, B., Xu, Y. FASEB J. (2005) [Pubmed]
  15. Homo- and hetero-dimerization of LPA/S1P receptors, OGR1 and GPR4. Zaslavsky, A., Singh, L.S., Tan, H., Ding, H., Liang, Z., Xu, Y. Biochim. Biophys. Acta (2006) [Pubmed]
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