Direct association of STAT3 with the IFNAR-1 chain of the human type I interferon receptor
Direct association of STAT3 with the IFNAR-1 chain of the human type I interferon receptor
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DOI：
10.1074/jbc.271.14.8057
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发表时间：
1996-04-05
影响因子：
4.8
通讯作者：
Pfeffer, LM
中科院分区：
文献类型：
--
作者：
Yang, CH;Shi, W;Pfeffer, LM
基于各种细胞因子激活转录因子STAT 3（信号转导和转录激活因子）或APRF（急性期反应因子）的报道，我们研究了STAT 3在I型干扰素（IFN）受体信号传导中的可能作用。我们表明，STAT 3经历IFN α依赖性酪氨酸磷酸化和IFN α治疗诱导蛋白质-DNA复合物，含有STAT 3。此外，在IFN α加入后，STAT 3以酪氨酸磷酸化依赖性方式与I型受体的IFNAR-1链结合。STAT 3与IFNAR-1链的结合通过STAT 3的含SH 2结构域部分与酪氨酸磷酸化的IFNAR-1链之间的直接相互作用发生。此外，与IFNAR-1链结合的酪氨酸磷酸化的STAT 3也经历了涉及丝氨酸磷酸化的二级修饰。这种磷酸化事件显然是由蛋白激酶C介导的，因为它被低浓度的蛋白激酶抑制剂H-7阻断。IFN激活STAT 3的生物学相关性进一步通过以下发现来说明：在对IFN α的抗病毒和抗增殖作用有抗性的细胞系中，STAT 3不被IFN激活，但其中JAK-STAT途径的其它组分被IFN α激活。
Based on the reports of the activation of the transcription factor known as STAT3 (for signal transducers and activators of transcription) or APRF (for acute phase response factor) by various cytokines, we investigated the possible role of STAT3 in type I interferon (IFN) receptor signaling. We show that STAT3 undergoes IFN alpha-dependent tyrosine phosphorylation and IFN alpha treatment induces protein-DNA complexes that contain STAT3. In addition, STAT3 associates with the IFNAR-1 chain of the type I receptor in a tyrosine phosphorylation-dependent manner upon IFN alpha addition. The binding of STAT3 to the IFNAR-1 chain occurs through a direct interaction between the SH2 domain-containing portion of STAT3 and the tyrosine-phosphorylated IFNAR-1 chain. Furthermore, tyrosine-phosphorylated STAT3 bound to the IFNAR-1 chain also undergoes a secondary modification involving serine phosphorylation. This phosphorylation event is apparently mediated by protein kinase C, since it was blocked by low concentrations of the protein kinase inhibitor H-7. The biological relevance of IFN activation of STAT3 is further illustrated by the finding that STAT3 is not activated by IFN in a cell line resistant to the antiviral and antiproliferative actions of IFN alpha but in which other components of the JAK-STAT pathway are activated by IFN alpha.