Follicle stimulating hormone (FSH) activates the p38 mitogen-activated protein kinase pathway, inducing small heat shock protein phosphorylation and cell rounding in immature rat ovarian granulosa cells.
Follicle stimulating hormone (FSH) activates the p38 mitogen-activated protein kinase pathway, inducing small heat shock protein phosphorylation and cell rounding in immature rat ovarian granulosa cells.
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DOI：
10.1210/endo.139.7.6188
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发表时间：
1998-07
期刊：
影响因子：
4.8
通讯作者：
E. Maizels;Joshua Cottom;Jonathan C. R. Jones;M. Hunzicker-Dunn
中科院分区：
文献类型：
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作者：
E. Maizels;Joshua Cottom;Jonathan C. R. Jones;M. Hunzicker-Dunn
本研究探讨了FSH激活未成熟颗粒细胞（GC）中p38丝裂原活化蛋白激酶（MAPK）通路的可能性。通过免疫沉淀和磷酸化特异性免疫印迹评价FSH诱导p38 MAPK磷酸化（活化）。用蛋白激酶A（PKA）抑制剂H89预处理可阻断FSH诱导的p38 MAPK磷酸化，并用cAMP生成激动剂forskolin模拟，表明FSH诱导的cAMP生成和PKA激活是GC中p38 MAPK激活的必要和充分条件。小热休克蛋白HSP-27包含p38 MAPK途径的下游磷酸化靶标。用p38 MAPK抑制剂SB 203580预处理可阻断FSH诱导的HSP-27磷酸化，表明p38 MAPK活化是FSH诱导的HSP-27磷酸化所必需的。用SB 203580预处理可阻断FSH诱导的GC变圆/聚集，表明p38 MAPK活化是FSH诱导的GC细胞形状改变所必需的。这些实验的结果表明，p38 MAPK途径在GC中以cAMP/PKA依赖性方式响应FSH而被激活，并且p38 MAPK活性是FSH诱导的HSP-27磷酸化以及GC中的圆化/聚集所必需的。
This study investigates the possibility that FSH activates the p38 mitogen-activated protein kinase (MAPK) pathway in immature granulosa cells (GC). FSH induced the phosphorylation (activation) of p38 MAPK as evaluated by immunoprecipitation and by phosphorylation-specific immunoblotting. FSH-induced phosphorylation of p38 MAPK was blocked by pretreatment with the protein kinase A (PKA) inhibitor H89 and mimicked by the cAMP generating agonist forskolin, indicating that FSH-induced cAMP production and PKA activation are necessary and sufficient for the activation of p38 MAPK in GC. The small heat shock protein HSP-27 comprises a downstream phosphorylation target for the p38 MAPK pathway. FSH-induced phosphorylation of HSP-27 was blocked by pretreatment with the p38 MAPK inhibitor SB 203580, indicating that p38 MAPK activation is necessary for FSH-induced HSP-27 phosphorylation. FSH-induced GC rounding/aggregation was blocked by pretreatment with SB 203580 indicating that p38 MAPK activation is necessary for FSH-induced GC cell shape change. The results of these experiments show that the p38 MAPK pathway is activated in GC in response to FSH in a cAMP/PKA-dependent manner, and that p38 MAPK activity is required for FSH-induced HSP-27 phosphorylation as well as rounding/aggregation in GC.