EP4 prostanoid receptor coupling to a pertussis toxin-sensitive inhibitory G protein
EP4 prostanoid receptor coupling to a pertussis toxin-sensitive inhibitory G protein
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DOI：
10.1124/mol.105.017749
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发表时间：
2006-01-01
影响因子：
3.6
通讯作者：
Regan, JW
中科院分区：
文献类型：
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作者：
Fujino, H;Regan, JW
EP2和EP4前列腺素受体亚型是前列腺素E-2（PGE（2））的G蛋白偶联受体。已知这两种受体亚型都与刺激性鸟嘌呤核苷酸结合蛋白（G α）偶联，在用PGE刺激后（2），可以增加细胞内cAMP的形成。此外，EP 4受体的PGE（2）刺激可以激活磷脂酰肌醇3-激酶（PI3K），导致细胞外信号调节激酶（ERK）的磷酸化和早期生长反应因子-1（EGR-1）的诱导（J Biol Chem 278：12151 - 12156，2003）。我们现在报道，PGE（2）介导的ERK磷酸化和EGR-1的诱导可以通过用百日咳毒素（PTX）预处理表达EP 4的细胞来阻断。此外，PTX预处理增加了表达EP 4的细胞中PGE（2）刺激的细胞内cAMP形成的量，但在表达EP 2的细胞中没有。这些数据表明，EP4前列腺素受体亚型，而不是EP2，耦合到PTX敏感的抑制性G蛋白（G α（i）），可以抑制cAMP依赖性信号传导和激活PI3K/ERK依赖性信号传导。
The EP2 and EP4 prostanoid receptor subtypes are G-protein-coupled receptors for prostaglandin E-2 (PGE(2)). Both receptor subtypes are known to couple to the stimulatory guanine nucleotide binding protein (G alpha(s)) and, after stimulation with PGE(2), can increase the formation of intracellular cAMP. In addition, PGE(2) stimulation of the EP4 receptor can activate phosphatidylinositol 3-kinase (PI3K) leading to phosphorylation of the extracellular signal-regulated kinases ( ERKs) and induction of early growth response factor-1 (EGR-1) (J Biol Chem 278: 12151 - 12156, 2003). We now report that the PGE(2)-mediated phosphorylation of the ERKs and induction of EGR-1 can be blocked by pretreatment of EP4-expressing cells with pertussis toxin (PTX). Furthermore, pretreatment with PTX increased the amount of PGE(2)-stimulated intracellular cAMP formation in EP4-expressing cells but not in EP2-expressing cells. These data indicate that the EP4 prostanoid receptor subtype, but not the EP2, couples to a PTX-sensitive inhibitory G-protein (G alpha(i)) that can inhibit cAMP-dependent signaling and activate PI3K/ERK-dependent signaling.