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LTB4R2  -  leukotriene B4 receptor 2

Homo sapiens

Synonyms: BLT2, BLT2R, BLTR2, JULF2, KPG_004, ...
 
 
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Disease relevance of LTB4R2

 

High impact information on LTB4R2

  • BLT2 is expressed ubiquitously, in contrast to BLT1, which is expressed predominantly in leukocytes [1].
  • The promoter region of the BLT1 gene is localized within the open reading frame (ORF) of the BLT2 gene, which encodes a low-affinity receptor for LTB(4) (Yokomizo, T., K. Kato, K. Terawaki, T. Izumi, and T. Shimizu. 2000. J. Exp. Med. 192:421-431) [4].
  • Several BLT1 antagonists, including U 75302, failed to inhibit LTB(4) binding to BLT2 [1].
  • The actions of LTB4 are mediated by two cell surface receptors, BLT1, which is predominantly expressed in peripheral blood leukocytes, and BLT2, which is expressed more ubiquitously [5].
  • Migration to LTB4 could be inhibited by either a BLT1- or BLT2-selective antagonist [5].
 

Biological context of LTB4R2

 

Anatomical context of LTB4R2

 

Associations of LTB4R2 with chemical compounds

  • We also show that 12(S)-hydroxyeicosatetraenoic acid, 12(S)-hydroperxyeicosatetraenoic acid, and 15(S)-hydroxyeicosatetraenoic acid competed with [(3)H]LTB(4) binding to BLT2, but not BLT1, dose dependently [11].
  • The antibodies did not cross-react with the recently cloned second LTB(4) receptor, BLTR2, or the Cys LT1 and Cys LT2 receptors [12].
  • On the other hand, Dex failed to enhance BLT2 expression in RA-differentiated HL-60 cells, indicating different transcriptional regulations for these two receptors in spite of the fact that their genes are closely located (J. Exp. Med. 192 (2000) 413-420) [13].
 

Other interactions of LTB4R2

  • BLT1 and BLT2 mRNA expression in synovial tissues was stronger in RA than in OA by real-time quantitative PCR [9].
  • BLT2 mRNA was strongly expressed in the synovial lining cells, which also expressed 5-lipoxygenase, an enzyme that synthesizes LTB4 [9].
  • Here we report the isolation of another gene encoding a functional G protein-coupled receptor for leukotriene B(4), named JULF2 [6].
  • BLT2 is the main receptor mediating the effects of LTB4 in the synovial tissues of patients with RA; this suggests the possibility of developing a new therapy to block LTB4 in inflammatory arthritis [9].
  • The actions of LTB(4) are mediated by the specific G protein-coupled receptors, BLT1 and BLT2 [13].
 

Analytical, diagnostic and therapeutic context of LTB4R2

  • Here, we report the molecular cloning of a novel GPCR for LTB(4), designated BLT2, which binds LTB(4) with a Kd value of 23 nM compared with 1.1 nM for BLT1, but still efficiently transduces intracellular signaling [1].
  • Finally, in situ hybridization analysis revealed that expression of BLT2 is significantly upregulated in a variety of human cancers [7].
  • We analyzed LTB4 receptors, BLT1 and BLT2, by using RT-PCR [14].
  • The genomic region containing the genes encoding the first leukotriene B(4) receptor, BLTR, as well as the recently cloned second leukotriene B(4)-activated receptor, BLTR2, was mapped by (a) sequence analysis of a human bacterial artificial chromosome (BAC) library containing a 15-kb segment corresponding to chromosome 14q11 [8].
  • The c-Myb protein (75 kDa) was detected in Pr2181 but not as a clear band in BLT2, while BTL-PC3 exhibited a 65-kDa c-Myb band in immunoprecipitation tests with anti-Myb antiserum [15].

References

  1. A second leukotriene B(4) receptor, BLT2. A new therapeutic target in inflammation and immunological disorders. Yokomizo, T., Kato, K., Terawaki, K., Izumi, T., Shimizu, T. J. Exp. Med. (2000) [Pubmed]
  2. Regulatory expression of lipoxin A4 receptor in physiologically estrus cycle and pathologically endometriosis. Motohashi, E., Kawauchi, H., Endo, H., Kondo, H., Kitasato, H., Kuramoto, H., Majima, M., Unno, N., Hayashi, I. Biomed. Pharmacother. (2005) [Pubmed]
  3. Specific expression of cellular oncogenes c-myc and c-myb in T-cell lines established from three types of bovine lymphosarcomas. Ishiguro, N., Matsui, T., Shinagawa, M. Am. J. Vet. Res. (1993) [Pubmed]
  4. Cell-specific transcriptional regulation of human leukotriene B(4) receptor gene. Kato, K., Yokomizo, T., Izumi, T., Shimizu, T. J. Exp. Med. (2000) [Pubmed]
  5. Leukotriene B4 receptors BLT1 and BLT2: expression and function in human and murine mast cells. Lundeen, K.A., Sun, B., Karlsson, L., Fourie, A.M. J. Immunol. (2006) [Pubmed]
  6. Molecular cloning and characterization of another leukotriene B4 receptor. Kamohara, M., Takasaki, J., Matsumoto, M., Saito, T., Ohishi, T., Ishii, H., Furuichi, K. J. Biol. Chem. (2000) [Pubmed]
  7. Role of the BLT2, a leukotriene B4 receptor, in Ras transformation. Yoo, M.H., Song, H., Woo, C.H., Kim, H., Kim, J.H. Oncogene (2004) [Pubmed]
  8. Genomic organization of the leukotriene B(4) receptor locus of human chromosome 14. Nilsson, N.E., Tryselius, Y., Owman, C. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  9. Differential expression of leukotriene B4 receptor subtypes (BLT1 and BLT2) in human synovial tissues and synovial fluid leukocytes of patients with rheumatoid arthritis. Hashimoto, A., Endo, H., Hayashi, I., Murakami, Y., Kitasato, H., Kono, S., Matsui, T., Tanaka, S., Nishimura, A., Urabe, K., Itoman, M., Kondo, H. J. Rheumatol. (2003) [Pubmed]
  10. Study of the role of leukotriene B()4 in abnormal function of human subchondral osteoarthritis osteoblasts: effects of cyclooxygenase and/or 5-lipoxygenase inhibition. Paredes, Y., Massicotte, F., Pelletier, J.P., Martel-Pelletier, J., Laufer, S., Lajeunesse, D. Arthritis Rheum. (2002) [Pubmed]
  11. Hydroxyeicosanoids bind to and activate the low affinity leukotriene B4 receptor, BLT2. Yokomizo, T., Kato, K., Hagiya, H., Izumi, T., Shimizu, T. J. Biol. Chem. (2001) [Pubmed]
  12. First-generation monoclonal antibodies identifying the human leukotriene B(4) receptor-1. Pettersson, A., Boketoft, A., Sabirsh, A., Nilsson, N.E., Kotarsky, K., Olde, B., Owman, C. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  13. Glucocorticoids up-regulate leukotriene B4 receptor-1 expression during neutrophilic differentiation of HL-60 cells. Obinata, H., Yokomizo, T., Shimizu, T., Izumi, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  14. Leukotriene B4 stimulates human monocyte-derived dendritic cell chemotaxis. Shin, E.H., Lee, H.Y., Bae, Y.S. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  15. A spontaneous internal deletion of the c-myb protooncogene enhances transcriptional activation in bovine T lymphoma cells. Ishiguro, N., Ohzono, T., Shinagawa, T., Horiuchi, M., Shinagawa, M. J. Biol. Chem. (1994) [Pubmed]
 
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