ERK2 mediates oxytocin-stimulated PGE2 synthesis.
ERK2 mediates oxytocin-stimulated PGE2 synthesis.
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ERK2 介导催产素刺激的 PGE2 合成。
DOI：
10.1152/ajpendo.1998.274.4.e634
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Soloff,MS
中科院分区：
文献类型：
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作者：
Strakova,Z;Copland,JA;Lolait,SJ;Soloff,MS
催产素(OT)诱导子宫内膜和羊膜细胞合成PG。我们先前的研究表明，稳定转染大鼠催产素受体的CHO细胞(CHO-OTR细胞)也能合成PGE2，以响应OT。在目前的工作中，我们已经证明了OTRs通过免疫沉淀和ADP核糖化作用与GiR和GQ/11偶联。OT处理引起细胞外信号调节蛋白激酶2(ERK2或p42MAPK)的快速磷酸化，并被百日咳毒素(PTX)部分抑制，这与OTR-Gicouble一致。Ptx不敏感的ERK2磷酸化部分与GQ相连，作为磷脂酶C(U-73122)和蛋白激酶C(GF-109203X)的抑制剂可阻断OT诱导的ERK2磷酸化。OT刺激的c-fos表达也是由ERK2磷酸化介导的。ERK-c-fos途径被证明与细胞增殖有关，但OT对CHO-OTR细胞摄取[~3H]胸腺嘧啶核苷没有影响。然而，用ERK激酶抑制剂(PD-98059)抑制OT诱导的ERK2的磷酸化显著减少OT刺激的PGE2的合成，表明ERK2的激活在OT作用中的重要性。
Oxytocin (OT) induces PG synthesis by both uterine endometrial and amnion cells. We showed previously that CHO cells stably transfected with the rat oxytocin receptor (CHO-OTR cells) also synthesize PGE2in response to OT. In the present work we have demonstrated that OTRs are coupled to both Giand Gq/11, using immunoprecipitation of solubilized OTR complexes and ADP ribosylation. OT treatment caused the rapid phosphorylation of extracellular signal-regulated protein kinase 2 (ERK2 or p42MAPK), which was partially inhibited by pertussis toxin (PTX), consistent with OTR-Gicoupling. The PTX-insensitive portion of ERK2 phosphorylation was linked to Gq, as inhibitors of both phospholipase C (U-73122) and protein kinase C (GF-109203X) blocked OT-induced ERK2 phosphorylation. OT-stimulatedc-fosexpression was also mediated by ERK2 phosphorylation. The ERK-c-fospathway has been shown to be associated with cell proliferation, but OT had no effect on [3H]thymidine uptake by CHO-OTR cells. However, inhibition of OT-induced ERK2 phosphorylation with an ERK kinase inhibitor (PD-98059) markedly reduced OT-stimulated PGE2synthesis, pointing to the importance of ERK2 activation in OT action.