© 2006 The Japanese Biochemical Society.
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5-Oxo-Eicosatetraenoic Acid-Induced Chemotaxis: Identification of a Responsible Receptor hGPCR48 and Negative Regulation by G Protein G12/13
1 Department of Nano-Material Systems, Gunma University Graduate School of Engineering, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515; 2 Department of Molecular Biochemistry, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511; 3 Institute for Bimolecular Science, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Tokyo 171-8588; and 4 Lead Discovery Research Laboratories, Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710
To whom correspondence should be addressed. Tel/Fax: +81-277-30-1434, E-mail: stakeda{at}bce.gunma-u.ac.jp
While screening genes encoding G protein–coupled receptors (GPCRs) in the human genome, we and other groups have identified a GPCR named hGPCR48 as a high affinity receptor for 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), which is arachidonic acid metabolite and an endogenous chemoattractant for granulocytes. Using Chinese hamster ovary (CHO) cells stably expressing hGPCR48, we show here that activation of the receptor causes the chemotaxis of the cells toward 5-oxo-ETE. We also show that the chemotaxis of human granulocytes toward 5-oxo-ETE is inhibited by pretreatment with anti-hGPCR48 antibodies, indicating that hGPCR48 is an endogenous receptor responsible for chemotaxis of granulocytes toward 5-oxo-ETE. In addition, we show that the chemotaxis of CHO cells expressing hGPCR48 is suppressed by pretreatment with pertussis toxin, and enhanced by overexpression of the carboxy terminal peptides of G
12/13 subunits or a regulator of the G protein signaling domain of p115RhoGEF, both of which are known to suppress G12/13-dependent signaling pathways. These results indicate that hGPCR48 couples with Gi/o and G12/13 proteins, which then initiate or attenuate the chemotaxis of the cells toward 5-oxo-ETE, respectively.