Platanias L C, Uddin S, Domanski P, Colamonici O R
Section of Hematology-Oncology, Department of Medicine, University of Illinois at Chicago, 60607, USA.
J Biol Chem. 1996 Sep 27;271(39):23630-3. doi: 10.1074/jbc.271.39.23630.
All Type I interferons (IFNalpha, IFNbeta, IFNomega) bind to the Type I IFN receptor (IFNR) and elicit a common set of signaling events, including activation of the Jak/Stat and IRS pathways. However, IFNbeta selectively induces the association of the alpha subunit of the Type I IFNR with p100, a tyrosyl phosphoprotein, to transduce IFNbeta-specific signals. Using antibodies raised against the different components of the Type I IFNR, we identified p100 as the long form of the beta subunit (betaL subunit) of the Type I IFNR. This was also confirmed in experiments with mouse L-929 cells transfected with truncated forms of betaL. Thus, IFNbeta stimulation of human cells or mouse L-929 transfectants expressing the human alpha and betaL subunits, selectively induces the formation of a signaling complex containing the alpha and betaL subunits of the receptor. The IFNbeta-regulated interaction of the alpha and betaL chains is rapid and transient and follows a similar time course with the tyrosine phosphorylation of these receptor components. These data demonstrate that the signaling specificity for different Type I IFNs is established early in the signaling cascade, at the receptor level, and results from distinct interactions between components of the Type I IFNR.
所有I型干扰素（IFNα、IFNβ、IFNω）均与I型干扰素受体（IFNR）结合，并引发一系列共同的信号转导事件，包括Jak/Stat和IRS信号通路的激活。然而，IFNβ可选择性地诱导I型IFNR的α亚基与一种酪氨酰磷酸化蛋白p100缔合，以转导IFNβ特异性信号。我们利用针对I型IFNR不同组分产生的抗体，将p100鉴定为I型IFNR的β亚基的长形式（βL亚基）。在用截短形式的βL转染的小鼠L-929细胞进行的实验中也证实了这一点。因此，IFNβ对表达人α亚基和βL亚基的人细胞或小鼠L-929转染细胞的刺激，选择性地诱导形成一种包含该受体α亚基和βL亚基的信号复合物。IFNβ调节的α链和βL链的相互作用迅速且短暂，并且与这些受体组分的酪氨酸磷酸化具有相似的时间进程。这些数据表明，不同I型干扰素的信号转导特异性在信号级联反应的早期、受体水平就已确立，并且是由I型IFNR各组分之间不同的相互作用所致。
