Estrogen receptor α rapidly activates the IGF-1 receptor pathway
Estrogen receptor α rapidly activates the IGF-1 receptor pathway
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DOI：
10.1074/jbc.m910345199
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发表时间：
2000-06-16
影响因子：
4.8
通讯作者：
Grohé, C
中科院分区：
文献类型：
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作者：
Kahlert, S;Nuedling, S;Grohé, C
雌激素和胰岛素样生长因子1（IGF-1）是有效的促有丝分裂刺激物，在控制细胞增殖方面具有重要的特性。然而，雌激素受体α和β与IGF-1受体（IGF-1 R）的信号级联之间的耦合知之甚少。因此，我们选择性地将雌激素受体α或β转染到含有IGF-1 R的COS 7和HEK 293细胞中。在雌激素受体α而非β存在的情况下，17 β-雌二醇（E2）迅速诱导IGF-IR和细胞外信号调节激酶1/2的磷酸化。此外，在用E2刺激后，雌激素受体α而非β迅速与COS 7和L 6细胞中的IGF-1 R结合，COS 7和L 6细胞内源性表达所有研究的受体，在IGF-1 R缺陷的成纤维细胞系R-中的对照实验表明，在用E2刺激后，只有雌激素受体α与转染的IGF-1 R结合，显性负性丝裂原活化蛋白激酶激酶的过表达抑制了这种作用，最后，在IGF-1刺激的细胞中，雌激素受体α而不是β是诱导雌激素受体反应性报告基因ERE-LUC活化所必需的。总之，这些数据表明，配体结合的雌激素受体α是快速激活IGF-1 R信号级联反应所必需的。
Estrogen and insulin-like-growth factor 1 (IGF-1) are potent mitogenic stimuli that share important properties in the control of cellular proliferation. However, the coupling between the signaling cascades of estrogen receptors alpha and beta and the IGF-1 receptor (IGF-1R) is poorly understood. Therefore, we selectively transfected estrogen receptor alpha or beta in COS7 and HEK293 cells, which contain IGF-1R. In presence of estrogen receptor alpha but not beta, 17 beta-estradiol (E2) rapidly induces phosphorylation of the IGF-IR and the extracellular signal-regulated kinases 1/2, Furthermore, upon stimulation with E2, estrogen receptor alpha but not beta bound rapidly to the IGF-1R in COS7 as well as L6 cells, which express all investigated receptors endogenously, Control experiments in the IGF-1R-deficient fibroblast cell line R- showed that after stimulation with E2 only estrogen receptor alpha bound to the transfected IGF-IR, Overexpression of dominant negative mitogen-activated protein kinases kinase inhibited this effect, Finally, estrogen receptor alpha but not beta is required to induce the activation of the estrogen receptor-responsive reporter ERE-LUC in IGF-1-stimulated cells. Taken together, these data demonstrate that ligand bound estrogen receptor alpha is required for rapid activation of the IGF-1R signaling cascade.