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Alternative splicing of C-terminal tail of prostaglandin E receptor subtype EP3 determines G-protein specificity

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Abstract

PEPTIDE hormones, neurotransmitters, and autacoids activate a family of seven-transmembrane-domain receptors1. Each of these receptors specifically couples to one of several G proteins, Gs, Gi, Go and Gp, to activate a specific second messenger system2. Cell surface receptors for prostanoids have been characterized pharmacologically3 and the complementary DNAs for thrombox-ane A2 receptor4,5 and the EP3 subtype of the prostaglandin (PG)E receptor6 reveal that they belong to the seven-transmembrane-domain receptor family. The EP3 receptor mediates the diverse physiological actions of PGE2 (ref. 3). Although most of them occur through coupling of the EP3 receptor to Gi and inhibition of adenylyl cyclase, the EP3-mediated contraction of uterine muscle can only occur by activation of another second messenger pathway7. In chromaffin cells, two different second messenger pathways are activated by PGE2 binding to an apparently single EP3 receptor class8. Here we show that at least four isoforms of the EP3 receptor, which differ only at their C-terminal tails and are produced by alternative splicing, couple to different G proteins to activate different second messenger systems.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606, Japan

    Tsunehisa Namba, Fumitaka Ushikubi, Akira Kakizuka & Shuh Narumiya

  2. Department of Anaesthesia, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606, Japan

    Tsunehisa Namba

  3. Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606, Japan

    Yukihiko Sugimoto, Manabu Negishi, Atsushi Irie & Atsushi Ichikawa

  4. The Osaka Bioscience Institute, Suita, Osaka, 565, Japan

    Seiji Ito

Authors
  1. Tsunehisa Namba
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  2. Yukihiko Sugimoto
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  3. Manabu Negishi
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  5. Fumitaka Ushikubi
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  6. Akira Kakizuka
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  7. Seiji Ito
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Namba, T., Sugimoto, Y., Negishi, M. et al. Alternative splicing of C-terminal tail of prostaglandin E receptor subtype EP3 determines G-protein specificity. Nature 365, 166–170 (1993). https://doi.org/10.1038/365166a0

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  • DOI: https://doi.org/10.1038/365166a0

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