Signal transducer and activator of transcription-3 serine phosphorylation by insulin is mediated by a Ras/Raf/MEK-dependent pathway
Signal transducer and activator of transcription-3 serine phosphorylation by insulin is mediated by a Ras/Raf/MEK-dependent pathway
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DOI：
10.1210/en.138.10.4131
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发表时间：
1997-10-01
期刊：
影响因子：
4.8
通讯作者：
Pessin, JE
中科院分区：
文献类型：
--
作者：
Ceresa, BP;Horvath, CM;Pessin, JE
我们最近报道了胰岛素刺激导致STAT3（转录-3的信号传感器和激活因子）的丝氨酸磷酸化。在本研究中，我们确定了727丝氨酸是胰岛素刺激下STAT3丝氨酸磷酸化的位点。这个磷酸化事件独立于酪氨酸磷酸化发生。此外，白细胞介素6诱导的酪氨酸磷酸化可以独立于丝氨酸磷酸化发生，表明这两种磷酸化途径在机制上是不相关的。异霉素选择性激活有丝分裂原活化蛋白（MAP）激酶的JNK和p38家族，不会导致STAT3的磷酸化。相反，胰岛素和渗透性休克激活ERK MAP激酶通路导致STAT3丝氨酸磷酸化。此外，显性干扰性Ras突变体（N17Ras）的表达或特定MEK抑制剂（PD98059）的处理阻止了胰岛素对STAT3丝氨酸磷酸化的刺激。通过表达MAP激酶磷酸酶（MKP-1）阻断ERK活化对胰岛素刺激的STAT3丝氨酸磷酸化没有影响。综上所述，这些数据表明胰岛素刺激的STAT3丝氨酸磷酸化是通过mek依赖性途径发生的，而该途径独立于ERK激活。
We recently reported that insulin stimulation results in the serine phosphorylation of STAT3 (signal transducer and activator of transcription-3). In the present study, we identified serine 727 as the site of insulin-stimulated STAT3 serine phosphorylation. This phosphorylation event occurs independent of tyrosine phosphorylation. Furthermore, interleukin-6-induced tyrosine phosphorylation can occur independent of serine phosphorylation, demonstrating that these two phosphorylation pathways are mechanistically unrelated. Selective activation of the JNK and p38 family of mitogen-activated protein (MAP) kinases by anisomycin treatment did not result in the phosphorylation of STAT3. In contrast, activation of the ERK MAP kinase pathway with both insulin and osmotic shock resulted in the serine phosphorylation of STAT3. In addition, expression of a dominant-interfering Ras mutant (N17Ras) or treatment with the specific MEK inhibitor (PD98059) prevented the insulin stimulation of STAT3 serine phosphorylation. Blockade of ERK activation by expression of the MAP kinase phosphatase (MKP-1) had no effect on insulin-stimulated STAT3 serine phosphorylation. Together, these data demonstrate that the insulin-stimulated serine phosphorylation of STAT3 occurs by a MEK-dependent pathway that is independent of ERK activation.