Induction of c-fos and c-jun messenger ribonucleic acid expression by prostaglandin F2alpha is mediated by a protein kinase C-dependent extracellular signal-regulated kinase mitogen-activated protein kinase pathway in bovine luteal cells.
Induction of c-fos and c-jun messenger ribonucleic acid expression by prostaglandin F2alpha is mediated by a protein kinase C-dependent extracellular signal-regulated kinase mitogen-activated protein kinase pathway in bovine luteal cells.
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前列腺素 F2α 诱导 c-fos 和 c-jun 信使核糖核酸表达是由牛黄体细胞中蛋白激酶 C 依赖性细胞外信号调节激酶丝裂原激活蛋白激酶途径介导的。
作者：
D. Chen;H. Fong;J. Davis
PGF 2 α触发黄体死亡，从而抑制孕酮合成，黄体结构退化，发情周期恢复。在与其异源三聚体G蛋白偶联受体结合后，PGF 2 α启动磷脂酶C/二酰基甘油和肌醇-1，4，5-三磷酸/Ca（2+）-蛋白激酶C（PKC）信号通路。最近，我们已经证明，PGF 2 α激活细胞外信号调节激酶（ERK）有丝分裂原激活蛋白（MAP）激酶信号通过Raf-dependent机制在牛黄体细胞。然而，PGF 2 α信号转导中PKC和ERK激活之间的关系尚未明确。此外，PGF 2 α用于调节基因表达的信号通路尚不清楚。在本报告中，牛黄体细胞的原代培养物被用来解决的作用，PKC在ERK激活和信号通路诱导的c-fos和c-jun信使RNA（mRNA）的表达，响应PGF 2 α。通过使用PKC抑制剂和PKC缺陷的黄体细胞模型，我们观察到PKC的佛波酯反应亚型是ERK磷酸化和PGF 2 α（1 μ M）或佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）（20 nM）激活所必需的。在PGF 2 α和PMA处理的细胞中，活性ERK MAP激酶位于细胞核中。PGF 2 α诱导的ERK磷酸化被MEK 1抑制剂PD 098059（1-50 μ M）剂量依赖性抑制。用PGF 2 α（1 μ M）或PMA（20 nM）处理30 min，可显著增加黄体细胞中c-fos和c-jun mRNA的表达。我们还观察到，ERK MAP激酶的激活是PGF 2 α和PMA应答c-fos和c-jun mRNA表达所必需的，因为用PD 098059阻断ERK通路可消除ERK MAP激酶的激活。此外，PGF 2 α和PMA诱导的c-fos和c-jun mRNA表达在PKC缺陷细胞中被消除。总之，我们的数据表明，PKC依赖的ERK MAP激酶途径介导的表达c-fos和c-jun在PGF 2 α处理的牛黄体细胞。
PGF2alpha triggers the demise of the corpus luteum whereby progesterone synthesis is inhibited, the luteal structure regresses, and the estrus cycle resumes. Upon binding to its heterotrimeric G-protein-coupled receptors, PGF2alpha initiates the phospholipase C/diacylglycerol and inositol-1,4,5-trisphosphate/Ca(2+)-protein kinase C (PKC) signaling pathway. More recently, we have demonstrated that PGF2alpha activates extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase signaling through a Raf-dependent mechanism in bovine luteal cells. However, the relationship between PKC and ERK activation in PGF2alpha signaling has not been clearly defined. Moreover, the signaling pathway that PGF2alpha uses to regulate gene expression is unknown. In this report, primary cultures of bovine luteal cells were used to address the role of PKC in ERK activation and the signaling pathway for induction of c-fos and c-jun messenger RNA (mRNA) expression in response to PGF2alpha. By using a PKC inhibitor and a PKC-deficient luteal cell model, we observed that phorbol ester-responsive isoforms of PKC were required for ERK phosphorylation and activation by PGF2alpha (1 microM) or phorbol 12-myristate 13-acetate (PMA) (20 nM). In PGF2alpha- and PMA-treated cells, active ERK MAP kinase was localized in the nucleus. PGF2alpha-induced ERK phosphorylation was dose-dependently inhibited by the MEK1 inhibitor PD098059 (1-50 microM). The expression of c-fos and c-jun mRNA in luteal cells was markedly increased by treatment with PGF2alpha (1 microM) or PMA (20 nM) for 30 min. We also observed that activation of ERK MAP kinase was required for the expression of c-fos and c-jun mRNA in response to PGF2alpha and PMA because it was abrogated by blocking the ERK pathway with PD098059. In addition, PGF2alpha and PMA-induced c-fos and c-jun mRNA expression was abolished in the PKC-deficient cells. Taken together, our data demonstrate that a PKC-dependent ERK MAP kinase pathway mediates the expression of c-fos and c-jun mRNA in PGF2alpha-treated bovine luteal cells.