Yang C H, Shi W, Basu L, Murti A, Constantinescu S N, Blatt L, Croze E, Mullersman J E, Pfeffer L M
Department of Pathology, University of Tennessee Health Science Center, Memphis, 38163, USA.
J Biol Chem. 1996 Apr 5;271(14):8057-61. doi: 10.1074/jbc.271.14.8057.
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 IFNalpha-dependent tyrosine phosphorylation and IFNalpha 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 IFNalpha 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 IFNalpha.
基于各种细胞因子激活转录因子STAT3（信号转导子和转录激活子3）或APRF（急性期反应因子）的报道，我们研究了STAT3在I型干扰素（IFN）受体信号传导中的可能作用。我们发现STAT3会发生IFNα依赖的酪氨酸磷酸化，并且IFNα处理会诱导形成含有STAT3的蛋白质-DNA复合物。此外，添加IFNα后，STAT3以酪氨酸磷酸化依赖的方式与I型受体的IFNAR-1链结合。STAT3与IFNAR-1链的结合是通过STAT3含SH2结构域的部分与酪氨酸磷酸化的IFNAR-1链之间的直接相互作用实现的。此外，与IFNAR-1链结合的酪氨酸磷酸化STAT3还会经历涉及丝氨酸磷酸化的二次修饰。这一磷酸化事件显然是由蛋白激酶C介导的，因为低浓度的蛋白激酶抑制剂H-7可阻断该过程。对一种对IFNα的抗病毒和抗增殖作用具有抗性，但JAK-STAT途径的其他成分可被IFNα激活的细胞系的研究发现，IFN无法激活其中的STAT3，这进一步说明了IFN激活STAT3的生物学意义。
