Growth hormone and erythropoietin differentially activate DNA-binding proteins by tyrosine phosphorylation.
Growth hormone and erythropoietin differentially activate DNA-binding proteins by tyrosine phosphorylation.
复制标题
生长激素和促红细胞生成素通过酪氨酸磷酸化差异激活 DNA 结合蛋白。
DOI：
10.1128/mcb.14.3.2113-2118.1994
复制
发表时间：
1994
影响因子：
5.3
通讯作者：
Silva,CM
中科院分区：
文献类型：
--
作者：
Finbloom,DS;Petricoin3rd,EF;Hackett,RH;David,M;Feldman,GM;Igarashi,K;Fibach,E;Weber,MJ;Thorner,MO;Silva,CM
生长激素(GH)和促红细胞生成素(EPO)与它们各自的受体结合，导致受体聚集和酪氨酸激酶的激活，从而启动一系列事件，不仅导致几种蛋白质的快速酪氨酸磷酸化，还导致早期反应基因的诱导。在这篇报道中，我们发现生长激素和促红细胞生成素诱导分子量分别为93 kDa、91 kDa和84 kDa的细胞蛋白的酪氨酸磷酸化，这些蛋白形成DNA结合复合体，该复合体识别具有c-fos等快速诱导基因共同特征的增强子。蛋白质复合体的组装需要酪氨酸磷酸化，这在添加配体后几分钟内发生。活化的复合体从胞浆移位到胞核。GH激活的蛋白质在抗原性上类似于P91，P91是一种由干扰素和其他细胞因子激活的几种转录复合体共有的蛋白质。相反，EPO激活的蛋白质与P91不同。这些发现为细胞因子诱导的细胞内信号通路奠定了基础，该通路始于配体诱导的受体聚集，激活了一个或多个酪氨酸激酶。这些数据首次证明GH和EPO激活的酪氨酸磷酸化蛋白可以特异性地识别明确定义的增强子，从而提供了一种将信号从膜快速传递到细胞核的机制。
Binding of growth hormone (GH) and erythropoietin (EPO) to their respective receptors results in receptor clustering and activation of tyrosine kinases that initiate a cascade of events resulting not only in the rapid tyrosine phosphorylation of several proteins but also in the induction of early-response genes. In this report, we show that GH and EPO induce the tyrosine phosphorylation of cellular proteins with molecular masses of 93 kDa and of 91 and 84 kDa, respectively, and that these proteins form DNA-binding complexes which recognize an enhancer that has features in common with several rapidly induced genes such as c-fos.Assembly of the protein complexes required tyrosine phosphorylation, which occurred within minutes after addition of ligand. The activated complexes translocated from the cytoplasm to the nucleus. The protein activated by GH is antigenically similar to p91, a protein common to several transcription complexes that are activated by interferons and other cytokines. In contrast, the proteins activated by EPO are distinct from p91. These findings establish the outlines for a cytokine-induced intracellular signaling pathway, which begins with ligand-induced receptor clustering that activates one or more tyrosine kinases. These data are the first to demonstrate that GH- and EPO-activated tyrosine-phosphorylated proteins can specifically recognize a well-defined enhancer and therefore provide a mechanism for rapidly transducing signals from the membrane to the nucleus.