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FFAR2  -  free fatty acid receptor 2

Homo sapiens

Synonyms: FFA2, FFA2R, Free fatty acid receptor 2, G-protein coupled receptor 43, GPCR43, ...
 
 
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Disease relevance of FFAR2

  • Short-chain fatty acids induce acute phosphorylation of the p38 mitogen-activated protein kinase/heat shock protein 27 pathway via GPR43 in the MCF-7 human breast cancer cell line [1].
  • In contrast, the highly selective expression of GPR43 in leukocytes, particularly polymorphonuclear cells, suggests a role in the recruitment of these cell populations toward sites of bacterial infection [2].
  • They exhibited, however, a differential coupling to G proteins; GPR41 coupled exclusively though the Pertussis toxin-sensitive Gi/o family, whereas GPR43 displayed a dual coupling through Gi/o and Pertussis toxin-insensitive Gq protein families [2].
  • These common themes implicate GPR40, GPR41 and GPR43 in playing significant roles in metabolic diseases, such as diabetes, obesity and the metabolic syndrome [3].
 

High impact information on FFAR2

  • These results suggest that LSSIG and GPR43 might play pivotal roles in differentiation and immune response of monocytes and granulocytes [4].
  • Cytokine-stimulation induced LSSIG and GPR43 in bone marrow cells, and monocytes and neutrophils, respectively [4].
  • GPR41 is related to GPR43 (52% similarity; 43% identity) and was activated by similar ligands but with differing specificity for carbon chain length, with pentanoate being the most potent agonist [5].
  • This activity was confirmed after transient transfection of GPR43 into mammalian cells using Ca(2+) mobilization and [(35)S]guanosine 5'-O-(3-thiotriphosphate) binding assays and by coexpression with GIRK G protein-regulated potassium channels in Xenopus laevis oocytes [5].
  • Acetate was more selective for GPR43, whereas butyrate and isobutyrate were more active on GPR41 [2].
 

Biological context of FFAR2

 

Anatomical context of FFAR2

 

Associations of FFAR2 with chemical compounds

 

Analytical, diagnostic and therapeutic context of FFAR2

  • GPR43 protein was detected by Western blot analysis in extracts of whole wall and separated mucosa, but not in muscle plus submucosa extracts [8].

References

  1. Short-chain fatty acids induce acute phosphorylation of the p38 mitogen-activated protein kinase/heat shock protein 27 pathway via GPR43 in the MCF-7 human breast cancer cell line. Yonezawa, T., Kobayashi, Y., Obara, Y. Cell. Signal. (2007) [Pubmed]
  2. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. Le Poul, E., Loison, C., Struyf, S., Springael, J.Y., Lannoy, V., Decobecq, M.E., Brezillon, S., Dupriez, V., Vassart, G., Van Damme, J., Parmentier, M., Detheux, M. J. Biol. Chem. (2003) [Pubmed]
  3. The G-protein-coupled receptor 40 family (GPR40-GPR43) and its role in nutrient sensing. Covington, D.K., Briscoe, C.A., Brown, A.J., Jayawickreme, C.K. Biochem. Soc. Trans. (2006) [Pubmed]
  4. LSSIG is a novel murine leukocyte-specific GPCR that is induced by the activation of STAT3. Senga, T., Iwamoto, S., Yoshida, T., Yokota, T., Adachi, K., Azuma, E., Hamaguchi, M., Iwamoto, T. Blood (2003) [Pubmed]
  5. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. Brown, A.J., Goldsworthy, S.M., Barnes, A.A., Eilert, M.M., Tcheang, L., Daniels, D., Muir, A.I., Wigglesworth, M.J., Kinghorn, I., Fraser, N.J., Pike, N.B., Strum, J.C., Steplewski, K.M., Murdock, P.R., Holder, J.C., Marshall, F.H., Szekeres, P.G., Wilson, S., Ignar, D.M., Foord, S.M., Wise, A., Dowell, S.J. J. Biol. Chem. (2003) [Pubmed]
  6. The relationship between the effects of short-chain fatty acids on intestinal motility in vitro and GPR43 receptor activation. Dass, N.B., John, A.K., Bassil, A.K., Crumbley, C.W., Shehee, W.R., Maurio, F.P., Moore, G.B., Taylor, C.M., Sanger, G.J. Neurogastroenterol. Motil. (2007) [Pubmed]
  7. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Nilsson, N.E., Kotarsky, K., Owman, C., Olde, B. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  8. Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. Karaki, S., Mitsui, R., Hayashi, H., Kato, I., Sugiya, H., Iwanaga, T., Furness, J.B., Kuwahara, A. Cell Tissue Res. (2006) [Pubmed]
 
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