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Gene Review

PTGDR2  -  prostaglandin D2 receptor 2

Homo sapiens

Synonyms: CD294, CRTH2, Chemoattractant receptor-homologous molecule expressed on Th2 cells, DL1R, DP2, ...
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Disease relevance of GPR44

  • 3. Functional studies demonstrated that PGD(2) activation of recombinant CRTH2 results in decrease of intracellular cAMP in a pertussis toxin-sensitive manner [1].
  • Furthermore, in atopic dermatitis patients, a preferential increase of CRTH2+ cells was noted within the disease-related cutaneous lymphocyte-associated antigen-positive, but not the cutaneous lymphocyte-associated antigen-negative, CD4+ lymphocyte compartment [2].
  • In 58 patients with septic shock, we observed a reduced CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) expression on Th2 lymphocytes and regulatory T cells in comparison with 39 healthy volunteers [3].
  • These findings implied the involvement of CRTH2 in mast cell-mediated immune responses such as allergic reactions [4].
  • Pharmacologically, rat CRTH2 stably transfected in mouse preB lymphoma L1.2 cells behaved very similar compared with the mouse and human orthologs, showing a binding affinity for PGD2 of 11 nM, a functional calcium mobilization when exposed to agonist, and similar sensitivity to agonists and antagonists [5].

High impact information on GPR44


Chemical compound and disease context of GPR44

  • CONCLUSIONS: Our experience suggests that the pathogenesis of eosinophilic otitis media is related to the pharmaceutical effects of ramatroban, i.e., inhibition of the thromboxane A(2) receptor (TP) and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) [9].

Biological context of GPR44

  • 3, GPR44 to chromosome 11q12-q13.3, and GPR45 to chromosome 2q11 [10].
  • Two PCR products partially encoding novel GPCRs, named GPR44 and GPR45, were discovered and used to isolate the full-length translational open reading frames from a human genomic library [10].
  • High and low affinity binding sites for PGD(2) were identified in the CRTH2 receptor population by saturation analysis with respective equilibrium dissociation constants (K(D)) of 2.5 and 109 nM [1].
  • 1. The recombinant human prostaglandin D(2) (PGD(2)) receptor, hCRTH2, has been expressed in HEK293(EBNA) and characterized with respect to radioligand binding and signal transduction properties [1].
  • Family-based analysis of asthma and two common SNPs [G1544C and G1651A (rs545659)] in the 3'-untranslated region of CRTH2 showed significant evidence of linkage in the presence of disequilibrium for the 1651G allele (P = 0.003) of SNP rs545659 [8].

Anatomical context of GPR44


Associations of GPR44 with chemical compounds


Physical interactions of GPR44

  • Therefore, we showed that CRTH2 can functionally couple to the G-protein G(alphai/o) [1].

Regulatory relationships of GPR44

  • Characterization of DP receptor null mice in which antigen-induced airway and inflammatory responses are attenuated and identification of CRTH2 as a novel PGD(2) receptor have shed light on the role of PGD(2) in the immune and inflammatory responses [14].
  • In the present study, the expression of chemokine receptor 5 (CCR5) as a Th1 marker and a chemoattractant receptor-homologs molecule expressed on Th2 cells (CRTH2) were investigated in order to analyze impaired Th1/Th2 responses in the colonic mucosa of UC patients [15].
  • 15d-PGJ2 was thought to exert its effects on cells exclusively through peroxisome proliferator-activated receptor-gamma (PPARgamma) and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), which are both expressed on human eosinophils [16].
  • We show that following in vitro stimulation with N. meningitidis serogroup B (MenB) antigens, approximately 66% of the dividing mucosal CD4(+)CD45RO(+) memory population express the Th1-associated IL18-R while the remainder express CRTH2, a Th2-associated marker [17].
  • Genetic Impact of Functional Single Nucleotide Polymorphisms in the 3'-UTR Region of the Chemoattractant Receptor Expressed on Th2 Cells (CRTH2) Gene on Asthma and Atopy in a Japanese Population [18].

Other interactions of GPR44

  • This revealed that the affinity of PGD(2) for CRTH2 is eight times less than its affinity for the DP receptor [1].
  • The receptor encoded by GPR34 is most similar to the P2Y receptor subfamily, while the receptor encoded by GPR44 is most similar to chemoattractant receptors [10].
  • We hypothesize that the restoration of CRTH2/CCR3 expression may be an indicator for optimal recovery after septic shock [3].
  • Inhibition of cytokine/chemokine secretion implicates at least in part DP, but not CRTH2 [19].
  • Pretreatment with ramatroban (CRTH2 antagonist) and AL8810 (FP antagonist) did not reduce the production of these cytokines [20].

Analytical, diagnostic and therapeutic context of GPR44

  • To investigate the structural determinants of CRTH2 ligand binding, we performed site-directed mutagenesis of putative mCRTH2 ligand-binding residues, and we evaluated mutant receptor ligand binding and functional properties [21].
  • Enzyme-linked immunosorbent assays show that they do not alter the total number of CRTH2 receptors on the cell surface [22].
  • Inflammatory cascades mediated by CRTH2 ligation may therefore represent an important early step in the elicitation and maintenance of Th2-dependent skin inflammation [23].
  • Method: The CRTH2/DP expression was examined by RT-PCR and flow-cytometric analysis [20].
  • We previously identified the mouse CRTH2 homolog of human CRTH2 and suggest that animal models would provide a clear understanding on the precise function of CRTH2 in allergic disorders [24].


  1. Molecular pharmacology of the human prostaglandin D2 receptor, CRTH2. Sawyer, N., Cauchon, E., Chateauneuf, A., Cruz, R.P., Nicholson, D.W., Metters, K.M., O'Neill, G.P., Gervais, F.G. Br. J. Pharmacol. (2002) [Pubmed]
  2. Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2 cells in patients with atopic dermatitis. Iwasaki, M., Nagata, K., Takano, S., Takahashi, K., Ishii, N., Ikezawa, Z. J. Invest. Dermatol. (2002) [Pubmed]
  3. The Th2 response as monitored by CRTH2 or CCR3 expression is severely decreased during septic shock. Venet, F., Lepape, A., Debard, A.L., Bienvenu, J., Bohé, J., Monneret, G. Clin. Immunol. (2004) [Pubmed]
  4. CRTH2, an orphan receptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s). Nagata, K., Hirai, H., Tanaka, K., Ogawa, K., Aso, T., Sugamura, K., Nakamura, M., Takano, S. FEBS Lett. (1999) [Pubmed]
  5. Chemoattractant receptor-homologous molecule expressed on Th2 cells activation in vivo increases blood leukocyte counts and its blockade abrogates 13,14-dihydro-15-keto-prostaglandin D2-induced eosinophilia in rats. Shichijo, M., Sugimoto, H., Nagao, K., Inbe, H., Encinas, J.A., Takeshita, K., Bacon, K.B., Gantner, F. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  6. Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells. Wang, Y.H., Ito, T., Wang, Y.H., Homey, B., Watanabe, N., Martin, R., Barnes, C.J., McIntyre, B.W., Gilliet, M., Kumar, R., Yao, Z., Liu, Y.J. Immunity (2006) [Pubmed]
  7. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. Hirai, H., Tanaka, K., Yoshie, O., Ogawa, K., Kenmotsu, K., Takamori, Y., Ichimasa, M., Sugamura, K., Nakamura, M., Takano, S., Nagata, K. J. Exp. Med. (2001) [Pubmed]
  8. Sequence variants of the gene encoding chemoattractant receptor expressed on Th2 cells (CRTH2) are associated with asthma and differentially influence mRNA stability. Huang, J.L., Gao, P.S., Mathias, R.A., Yao, T.C., Chen, L.C., Kuo, M.L., Hsu, S.C., Plunkett, B., Togias, A., Barnes, K.C., Stellato, C., Beaty, T.H., Huang, S.K. Hum. Mol. Genet. (2004) [Pubmed]
  9. Successful treatment of eosinophilic otitis media using ramatroban: Report of two cases. Wada, T., Uemaetomari, I., Murashita, H., Tobita, T., Tsuji, S., Tabuchi, K., Okubo, H., Hara, A. Auris, nasus, larynx. (2006) [Pubmed]
  10. Discovery of three novel orphan G-protein-coupled receptors. Marchese, A., Sawzdargo, M., Nguyen, T., Cheng, R., Heng, H.H., Nowak, T., Im, D.S., Lynch, K.R., George, S.R., O'dowd, B.F. Genomics (1999) [Pubmed]
  11. Selective expression of a novel surface molecule by human Th2 cells in vivo. Nagata, K., Tanaka, K., Ogawa, K., Kemmotsu, K., Imai, T., Yoshie, O., Abe, H., Tada, K., Nakamura, M., Sugamura, K., Takano, S. J. Immunol. (1999) [Pubmed]
  12. 11-Dehydro-thromboxane B2, a stable thromboxane metabolite, is a full agonist of chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) in human eosinophils and basophils. Böhm, E., Sturm, G.J., Weiglhofer, I., Sandig, H., Shichijo, M., McNamee, A., Pease, J.E., Kollroser, M., Peskar, B.A., Heinemann, A. J. Biol. Chem. (2004) [Pubmed]
  13. Cutting edge: agonistic effect of indomethacin on a prostaglandin D2 receptor, CRTH2. Hirai, H., Tanaka, K., Takano, S., Ichimasa, M., Nakamura, M., Nagata, K. J. Immunol. (2002) [Pubmed]
  14. Hematopoietic prostaglandin D synthase. Kanaoka, Y., Urade, Y. Prostaglandins Leukot. Essent. Fatty Acids (2003) [Pubmed]
  15. Differential expression of CCR5 and CRTH2 on infiltrated cells in colonic mucosa of patients with ulcerative colitis. Matsuzaki, K., Hokari, R., Kato, S., Tsuzuki, Y., Tanaka, H., Kurihara, C., Iwai, A., Kawaguchi, A., Nagao, S., Itoh, K., Nagata, K., Miura, S. J. Gastroenterol. Hepatol. (2003) [Pubmed]
  16. Physiological levels of 15-deoxy-Delta12,14-prostaglandin J2 prime eotaxin-induced chemotaxis on human eosinophils through peroxisome proliferator-activated receptor-gamma ligation. Kobayashi, Y., Ueki, S., Mahemuti, G., Chiba, T., Oyamada, H., Saito, N., Kanda, A., Kayaba, H., Chihara, J. J. Immunol. (2005) [Pubmed]
  17. Regulation of Th-1 T cell-dominated immunity to Neisseria meningitidis within the human mucosa. Davenport, V., Groves, E., Hobbs, C.G., Williams, N.A., Heyderman, R.S. Cell. Microbiol. (2007) [Pubmed]
  18. Genetic Impact of Functional Single Nucleotide Polymorphisms in the 3'-UTR Region of the Chemoattractant Receptor Expressed on Th2 Cells (CRTH2) Gene on Asthma and Atopy in a Japanese Population. Maeda, Y., Hizawa, N., Takahashi, D., Fukui, Y., Konno, S., Nishimura, M. Int. Arch. Allergy Immunol. (2007) [Pubmed]
  19. Prostaglandin D2 affects the maturation of human monocyte-derived dendritic cells: consequence on the polarization of naive Th cells. Gosset, P., Bureau, F., Angeli, V., Pichavant, M., Faveeuw, C., Tonnel, A.B., Trottein, F. J. Immunol. (2003) [Pubmed]
  20. Prostaglandin D(2) Induces IL-8 and GM-CSF by Bronchial Epithelial Cells in a CRTH2-Independent Pathway. Chiba, T., Kanda, A., Ueki, S., Ito, W., Kamada, Y., Oyamada, H., Saito, N., Kayaba, H., Chihara, J. Int. Arch. Allergy Immunol. (2006) [Pubmed]
  21. Identification of determinants of ligand binding affinity and selectivity in the prostaglandin D2 receptor CRTH2. Hata, A.N., Lybrand, T.P., Breyer, R.M. J. Biol. Chem. (2005) [Pubmed]
  22. Identification of indole derivatives exclusively interfering with a G protein-independent signaling pathway of the prostaglandin D2 receptor CRTH2. Mathiesen, J.M., Ulven, T., Martini, L., Gerlach, L.O., Heinemann, A., Kostenis, E. Mol. Pharmacol. (2005) [Pubmed]
  23. CRTH2 is a prominent effector in contact hypersensitivity-induced neutrophil inflammation. Takeshita, K., Yamasaki, T., Nagao, K., Sugimoto, H., Shichijo, M., Gantner, F., Bacon, K.B. Int. Immunol. (2004) [Pubmed]
  24. Gene structure and functional properties of mouse CRTH2, a prostaglandin D2 receptor. Hirai, H., Abe, H., Tanaka, K., Takatsu, K., Sugamura, K., Nakamura, M., Nagata, K. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
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