ALTERNATIVE SPLICING OF C-TERMINAL TAIL OF PROSTAGLANDIN-E RECEPTOR SUBTYPE-EP3 DETERMINES G-PROTEIN SPECIFICITY
ALTERNATIVE SPLICING OF C-TERMINAL TAIL OF PROSTAGLANDIN-E RECEPTOR SUBTYPE-EP3 DETERMINES G-PROTEIN SPECIFICITY
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DOI：
10.1038/365166a0
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发表时间：
1993-09-09
期刊：
影响因子：
64.8
通讯作者：
NARUMIYA, S
中科院分区：
文献类型：
--
作者：
NAMBA, T;SUGIMOTO, Y;NARUMIYA, S
肽类激素、神经递质和自育激素激活一个七跨膜结构域受体家族1。这些受体中的每一种都特异性地与几种G蛋白G（s）、G（i）、G（o）和G（p）中的一种偶联，以激活特定的第二信使系统2。前列腺素类的细胞表面受体已在药理学上进行了表征3，血栓素A2受体4、5和前列腺素（PG）E受体6的EP 3亚型的互补DNA表明，它们属于七跨膜结构域受体家族。EP 3受体介导PGE 2的多种生理作用（参考文献3）。虽然它们中的大多数通过EP 3受体与G（i）的偶联和腺苷酸环化酶的抑制而发生，但EP 3介导的子宫肌肉收缩只能通过另一个第二信使途径的激活而发生7。在嗜铬细胞中，两种不同的第二信使途径被PGE 2与一种明显单一的EP 3受体class 8结合激活。在这里，我们表明，至少有四种亚型的EP 3受体，不同的只是在其C-末端的尾巴，并通过选择性剪接产生，耦合到不同的G蛋白激活不同的第二信使系统。
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, G(s), G(i), G(o) and G(p), to activate a specific second messenger system2. Cell surface receptors for prostanoids have been characterized pharmacologically3 and the complementary DNAs for thromboxane 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 G(i) 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.