Ceresa B P, Horvath C M, Pessin J E
Department of Physiology and Biophysics, University of Iowa, Iowa City 52242, USA.
Endocrinology. 1997 Oct;138(10):4131-7. doi: 10.1210/endo.138.10.5266.
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.
我们最近报道，胰岛素刺激会导致信号转导和转录激活因子3（STAT3）的丝氨酸磷酸化。在本研究中，我们确定丝氨酸727是胰岛素刺激的STAT3丝氨酸磷酸化位点。该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独立于丝氨酸磷酸化发生，表明这两条磷酸化途径在机制上不相关。茴香霉素处理对丝裂原活化蛋白（MAP）激酶的JNK和p38家族的选择性激活并未导致STAT3的磷酸化。相反，胰岛素和渗透压休克对ERK MAP激酶途径的激活导致了STAT3的丝氨酸磷酸化。此外，显性干扰Ras突变体（N17Ras）的表达或用特异性MEK抑制剂（PD98059）处理可阻止胰岛素对STAT3丝氨酸磷酸化的刺激。通过表达MAP激酶磷酸酶（MKP-1）对ERK激活的阻断对胰岛素刺激的STAT3丝氨酸磷酸化没有影响。总之，这些数据表明，胰岛素刺激的STAT3丝氨酸磷酸化是通过一条独立于ERK激活的MEK依赖性途径发生的。
