Platanias L C, Domanski P, Nadeau O W, Yi T, Uddin S, Fish E, Neel B G, Colamonici O R
Section of Hematology/Oncology, University of Illinois at Chicago, and West Side Veterans Affairs Hospital, Chicago, Illinois 60607, USA.
J Biol Chem. 1998 Mar 6;273(10):5577-81. doi: 10.1074/jbc.273.10.5577.
Expression of human alpha and long form of the beta (betaL) subunits of type I interferon receptor (IFN-R) in mouse cells is sufficient to activate the Jak-Stat pathway and to elicit an antiviral state in response to human IFNalpha2 and IFNbeta. We demonstrate herein, however, that these cells respond to the antiproliferative effects of murine IFNalphabeta but not human type I IFNs. These results suggest that an unknown species-specific component is required for the antiproliferative effect of human type I IFNs. The absence of this component can be complemented by expressing the human betaL chain truncated at amino acid 346. Thus, the distal region of betaL appears to function as a negative regulator of the growth inhibitory effects of type I IFNs. Further studies looking for possible targets of the betaL regulatory domain demonstrated that this region associates with a tyrosine phosphatase. These results suggest that a protein associated with the negative regulatory domain of betaL, likely a tyrosine phosphatase, plays a role in regulating the growth inhibitory effects of human type I IFNs.
I型干扰素受体（IFN-R）的人α亚基和长形式β亚基（βL）在小鼠细胞中的表达足以激活Jak-Stat信号通路，并在响应人IFNα2和IFNβ时引发抗病毒状态。然而，我们在此证明，这些细胞对鼠IFNαβ的抗增殖作用有反应，但对人I型干扰素没有反应。这些结果表明，人I型干扰素的抗增殖作用需要一种未知的物种特异性成分。通过表达在氨基酸346处截断的人βL链，可以弥补这种成分的缺失。因此，βL的远端区域似乎作为I型干扰素生长抑制作用的负调节因子发挥作用。进一步寻找βL调节域可能靶点的研究表明，该区域与一种酪氨酸磷酸酶相关联。这些结果表明，与βL负调节域相关的一种蛋白质，可能是一种酪氨酸磷酸酶，在调节人I型干扰素的生长抑制作用中发挥作用。
