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首页> 外文期刊>Molecular and Cellular Biology >Insulin-stimulated oocyte maturation requires insulin receptor substrate 1 and interaction with the SH2 domains of phosphatidylinositol 3-kinase.
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Insulin-stimulated oocyte maturation requires insulin receptor substrate 1 and interaction with the SH2 domains of phosphatidylinositol 3-kinase.

机译：胰岛素刺激的卵母细胞成熟需要胰岛素受体底物1并与磷脂酰肌醇3激酶的SH2结构域相互作用。

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Xenopus oocytes from unprimed frogs possess insulin-like growth factor I (IGF-I) receptors but lack insulin and IGF-I receptor substrate 1 (IRS-1), the endogenous substrate of this kinase, and fail to show downstream responses to hormonal stimulation. Microinjection of recombinant IRS-1 protein enhances insulin-stimulated phosphatidylinositol (PtdIns) 3-kinase activity and restores the germinal vesicle breakdown response. Activation of PtdIns 3-kinase results from formation of a complex between phosphorylated IRS-1 and the p85 subunit of PtdIns 3-kinase. Microinjection of a phosphonopeptide containing a pYMXM motif with high affinity for the src homology 2 (SH2) domain of PtdIns 3-kinase p85 inhibits IRS-1 association with and activation of the PtdIns 3-kinase. Formation of the IRS-1-PtdIns 3-kinase complex and insulin-stimulated PtdIns 3-kinase activation are also inhibited by microinjection of a glutathione S-transferase fusion protein containing the SH2 domain of p85. This effect occurs in a concentration-dependent fashion and results in a parallel loss of hormone-stimulated oocyte maturation. These inhibitory effects are specific and are not mimicked by glutathione S-transferase fusion proteins expressing the SH2 domains of ras-GAP or phospholipase C gamma. Moreover, injection of the SH2 domains of p85, ras-GAP, and phospholipase C gamma do not interfere with progesterone-induced oocyte maturation. These data demonstrate that phosphorylation of IRS-1 plays an essential role in IGF-I and insulin signaling in oocyte maturation and that this effect occurs through interactions of the phosphorylated YMXM/YXXM motifs of IRS-1 with SH2 domains of PtdIns 3-kinase or some related molecules.
机译：来自未启动青蛙的非洲爪蟾卵母细胞具有胰岛素样生长因子I（IGF-1）受体，但缺乏胰岛素和该激酶的内源性基质IGF-1受体底物1（IRS-1），并且无法显示出对激素刺激的下游反应。显微注射重组IRS-1蛋白可增强胰岛素刺激的磷脂酰肌醇（PtdIns）3激酶活性，并恢复发芽囊泡的分解反应。 PtdIns 3-激酶的激活是由于磷酸化的IRS-1与PtdIns 3-激酶的p85亚基之间形成复合物而引起的。显微注射含有对PtdIns 3-激酶p85的src同源2（SH2）域具有高亲和力的pYMXM基序的磷酸肽，可以抑制IRS-1与PtdIns 3-激酶的缔合和激活。 IRS-1-PtdIns 3激酶复合物的形成和胰岛素刺激的PtdIns 3激酶的激活也可以通过微注射含有p85 SH2域的谷胱甘肽S-转移酶融合蛋白来抑制。这种作用以浓度依赖性的方式发生，并导致激素刺激的卵母细胞成熟的平行损失。这些抑制作用是特异性的，不能被表达ras-GAP或磷脂酶Cγ的SH2结构域的谷胱甘肽S-转移酶融合蛋白所模仿。而且，注射p85，ras-GAP和磷脂酶Cγ的SH2结构域不会干扰孕激素诱导的卵母细胞成熟。这些数据表明，IRS-1的磷酸化在卵母细胞成熟中的IGF-I和胰岛素信号传导中起着至关重要的作用，并且这种作用是通过IRS-1的磷酸化YMXM / YXXM基序与PtdIns 3-激酶的SH2域相互作用而发生的。一些相关的分子。

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