Novel signal transduction pathway for luteinizing hormone and its interaction with insulin: Activation of janus kinase/signal transducer and activator of transcription and phosphoinositol 3-kinase/akt pathways
Novel signal transduction pathway for luteinizing hormone and its interaction with insulin: Activation of janus kinase/signal transducer and activator of transcription and phosphoinositol 3-kinase/akt pathways
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DOI：
10.1210/en.2002-220706
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发表时间：
2003-02-01
期刊：
影响因子：
4.8
通讯作者：
Saad, MJA
中科院分区：
文献类型：
--
作者：
Carvalho, CRO;Carvalheira, JBC;Saad, MJA
促黄体生成素（LH）的作用是通过一类细胞表面的LH/人绒毛膜促性腺激素受体介导的，该受体是G蛋白偶联受体家族的成员。在本研究中，我们发现LH可诱导大鼠卵巢中Janus激酶2（JAK2）迅速发生酪氨酸磷酸化并激活。JAK2激活后，检测到信号转导子和转录激活子-1（STAT - 1）、STAT - 5b、胰岛素受体底物-1（IRS - 1）以及Src同源区和胶原同源区（Shc）发生酪氨酸磷酸化。此外，LH分别诱导了IRS - 1/磷脂酰肌醇3 - 激酶以及Shc/生长因子受体结合蛋白2（Grb2）的结合，以及下游的AKT（蛋白激酶B，与v - AKT同源）丝氨酸磷酸化和细胞外调节蛋白激酶（ERK）酪氨酸磷酸化。在正常大鼠的整个卵巢中，同时注入胰岛素和LH比单独使用每种激素诱导出更高水平的JAK2、STAT5b、IRS - 1和AKT磷酸化。通过免疫组织化学方法，我们证明这些后期事件发生在卵泡细胞以及内外膜细胞中。这些结果表明了LH的一种新的信号转导途径，并显示在该组织中，胰岛素和LH信号通路在磷脂酰肌醇3 - 激酶/AKT通路水平上存在正性相互作用。
The actions of LH are mediated through a single class of cell surface LH/human chorionic gonadotropin receptor, which is a member of the G protein-coupled receptor family. In the present study we showed that LH induced rapid tyrosine phosphorylation and activation of the Janus kinase 2 (JAK2) in rat ovary. Upon JAK2 activation, tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT-1), STAT-5b, insulin receptor substrate-1 (IRS-1), and Src homology and collagen homology (Shc) were detected. In addition, LH induced IRS-1/phosphoinositol 3-kinase and Shc/growth factor receptor-binding protein 2 (Grb2) associations and downstream AKT (protein kinase B, homologous to v-AKT) serine phosphorylation and ERK tyrosine phosphorylation, respectively. The simultaneous infusion of insulin and LH induced higher phosphorylation levels of JAK2, STAT5b, IRS-1, and AKT compared with each hormone alone in the whole ovary of normal rats. By immunohistochemistry we demonstrated that these late events take place in follicular cells and both external and internal theca. These results indicate a new signal transduction pathway for LH and show that there is positive cross-talk between the insulin and LH signaling pathways at the level of phosphoinositol 3-kinase/AKT pathway in this tissue.