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Gene Review

GPR132  -  G protein-coupled receptor 132

Homo sapiens

Synonyms: G2 accumulation protein, G2A
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Disease relevance of GPR132


High impact information on GPR132

  • Incubation with an antibody to the LPC receptor, G2A, inhibited LPC-induced protection from CLP lethality and inhibited the effects of LPC in neutrophils [6].
  • Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A [1].
  • We show that LPC is a high-affinity ligand for G2A, a lymphocyte-expressed G protein-coupled receptor whose genetic ablation results in the development of autoimmunity [1].
  • Activation of G2A by LPC increased intracellular calcium concentration, induced receptor internalization, activated ERK mitogen-activated protein kinase, and modified migratory responses of Jurkat T lymphocytes [1].
  • However, in contrast to adriamycin, a marked phase-dependent sensitivity for the induction of G2-accumulation was observed; cells treated in early and mid-S-phase were most sensitive [7].

Chemical compound and disease context of GPR132


Biological context of GPR132


Anatomical context of GPR132


Associations of GPR132 with chemical compounds

  • However, we found the activity of the human G2A receptor and its mouse homolog to be significantly less sensitive to pH fluctuations as measured by inositol phosphate and cAMP accumulation [14].
  • G2A is a proton-sensing G-protein-coupled receptor antagonized by lysophosphatidylcholine [16].
  • Oxidized phosphatidylcholine (1-palmitoyl-2-linoleoyl) when hydrolyzed with phospholipase A(2) also evoked intracellular calcium mobilization in G2A-expressing cells [11].
  • Furthermore, G2A was activated by various oxidized derivatives of linoleic and arachidonic acids, but it was weakly activated by cholesteryl-9-HODE [11].
  • Rescue from G2A-induced apoptosis was achieved by co-expression of a G alpha(12/13)-specific inhibitor, p115RGS (regulator of G protein signaling), in combination with 2',5'-dideoxyadenosine treatment [10].

Other interactions of GPR132

  • As OGR1 and GPR4 were reported as proton-sensing GPCRs (Ludwig, M. G., Vanek, M., Guerini, D., Gasser, J. A., Jones, C. E., Junker, U., Hofstetter, H., Wolf, R. M., and Seuwen, K. (2003) Nature 425, 93-98), we evaluated the proton-sensing function of G2A [16].
  • The original publications describing GPR4, OGR1, and G2A as receptors for LPC or SPC have now been retracted, and the first studies exploring receptors of this family as pH sensors in physiology have appeared [17].
  • Degradation of exogenous p21 led to a shift to G2 accumulation in the cells exposed to BL [18].
  • In addition, HSC536N (+FAC) cells showed a twofold lower G2 accumulation following MMC treatment [19].
  • After UVC irradiation, synchronized gelsolin-overexpressing UMUC2 cells had a prolonged S phase followed by delayed G2 accumulation compared to neotransfected UMUC2 cells as determined by cell cycle analysis [20].

Analytical, diagnostic and therapeutic context of GPR132


  1. Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A. Kabarowski, J.H., Zhu, K., Le, L.Q., Witte, O.N., Xu, Y. Science (2001) [Pubmed]
  2. Human immunodeficiency virus type 1 cell cycle control: Vpr is cytostatic and mediates G2 accumulation by a mechanism which differs from DNA damage checkpoint control. Bartz, S.R., Rogel, M.E., Emerman, M. J. Virol. (1996) [Pubmed]
  3. Effect of melphalan and hyperthermia on cell cycle progression and cyclin B1 expression in human melanoma cells. Orlandi, L., Zaffaroni, N., Bearzatto, A., Costa, A., Supino, R., Vaglini, M., Silvestrini, R. Cell Prolif. (1995) [Pubmed]
  4. Sequence variability of human cytomegalovirus UL146 and UL147 genes in low-passage clinical isolates. He, R., Ruan, Q., Qi, Y., Ma, Y.P., Huang, Y.J., Sun, Z.R., Ji, Y.H. Intervirology (2006) [Pubmed]
  5. Mn-superoxide dismutase overexpression enhances G2 accumulation and radioresistance in human oral squamous carcinoma cells. Kalen, A.L., Sarsour, E.H., Venkataraman, S., Goswami, P.C. Antioxid. Redox Signal. (2006) [Pubmed]
  6. Therapeutic effects of lysophosphatidylcholine in experimental sepsis. Yan, J.J., Jung, J.S., Lee, J.E., Lee, J., Huh, S.O., Kim, H.S., Jung, K.C., Cho, J.Y., Nam, J.S., Suh, H.W., Kim, Y.H., Song, D.K. Nat. Med. (2004) [Pubmed]
  7. Kinetic response to cultured human lymphoid cells to rubidazone. Barlogie, B., Drewinko, B., Benjamin, R.S. J. Natl. Cancer Inst. (1978) [Pubmed]
  8. Lysophosphatidylcholine as a ligand for immunoregulation. Kabarowski, J.H., Xu, Y., Witte, O.N. Biochem. Pharmacol. (2002) [Pubmed]
  9. A DNA damage and stress inducible G protein-coupled receptor blocks cells in G2/M. Weng, Z., Fluckiger, A.C., Nisitani, S., Wahl, M.I., Le, L.Q., Hunter, C.A., Fernal, A.A., Le Beau, M.M., Witte, O.N. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  10. The lysophospholipid receptor G2A activates a specific combination of G proteins and promotes apoptosis. Lin, P., Ye, R.D. J. Biol. Chem. (2003) [Pubmed]
  11. Identification of 9-hydroxyoctadecadienoic acid and other oxidized free fatty acids as ligands of the G protein-coupled receptor G2A. Obinata, H., Hattori, T., Nakane, S., Tatei, K., Izumi, T. J. Biol. Chem. (2005) [Pubmed]
  12. 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]
  13. Positron emission tomography imaging analysis of G2A as a negative modifier of lymphoid leukemogenesis initiated by the BCR-ABL oncogene. Le, L.Q., Kabarowski, J.H., Wong, S., Nguyen, K., Gambhir, S.S., Witte, O.N. Cancer Cell (2002) [Pubmed]
  14. Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells. Radu, C.G., Nijagal, A., McLaughlin, J., Wang, L., Witte, O.N. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  15. Human resting CD16-, CD16+ and IL-2-, IL-12-, IL-15- or IFN-alpha-activated natural killer cells differentially respond to sphingosylphosphorylcholine, lysophosphatidylcholine and platelet-activating factor. Jin, Y., Damaj, B.B., Maghazachi, A.A. Eur. J. Immunol. (2005) [Pubmed]
  16. G2A is a proton-sensing G-protein-coupled receptor antagonized by lysophosphatidylcholine. Murakami, N., Yokomizo, T., Okuno, T., Shimizu, T. J. Biol. Chem. (2004) [Pubmed]
  17. Receptors for protons or lipid messengers or both? Seuwen, K., Ludwig, M.G., Wolf, R.M. J. Recept. Signal Transduct. Res. (2006) [Pubmed]
  18. The cyclin-dependent kinase inhibitor butyrolactone is a potent inhibitor of p21 (WAF1/CIP1 expression). Sax, J.K., Dash, B.C., Hong, R., Dicker, D.T., El-Deiry, W.S. Cell Cycle (2002) [Pubmed]
  19. The effect of the Fanconi anemia polypeptide, FAC, upon p53 induction and G2 checkpoint regulation. Kupfer, G.M., D'Andrea, A.D. Blood (1996) [Pubmed]
  20. Enhancement of G2 checkpoint function by gelsolin transfection in human cancer cells. Sakai, N., Ohtsu, M., Fujita, H., Koike, T., Kuzumaki, N. Exp. Cell Res. (1999) [Pubmed]
  21. Expression of G2A, a receptor for lysophosphatidylcholine, by macrophages in murine, rabbit, and human atherosclerotic plaques. Rikitake, Y., Hirata, K., Yamashita, T., Iwai, K., Kobayashi, S., Itoh, H., Ozaki, M., Ejiri, J., Shiomi, M., Inoue, N., Kawashima, S., Yokoyama, M. Arterioscler. Thromb. Vasc. Biol. (2002) [Pubmed]
  22. The action mode of lysophosphatidylcholine in human monocytes. Yun, M.R., Okajima, F., Im, D.S. J. Pharmacol. Sci. (2004) [Pubmed]
  23. Quantitative analysis of orphan G protein-coupled receptor mRNAs by TaqMan Real-Time PCR: G2A and GPR4 lysophospholipid receptor expression in leukocytes and in a rat myocardial infarction-heart failure model. Douglas, S.A., Ao, Z., Johns, D.G., Maniscalco, K., Willette, R.N., Sarov-Blat, L., Cogswell, J.P., Seepersaud, S., Murdock, P., Steplewski, K.M., Patel, L. Methods Mol. Biol. (2005) [Pubmed]
  24. Effect of hyperthermia on cyclin B expression in a human glioblastoma cell line. Ohshita, N., Nishizaki, T., Ishihara, H., Ito, H., Murakami, T., Mimura, Y. J. Neurooncol. (1995) [Pubmed]
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