Receptors for human alpha interferon: are gangliosides involved?
Receptors for human alpha interferon: are gangliosides involved?
复制标题
人α干扰素受体：神经节苷脂参与其中吗？
DOI：
10.1089/jir.1984.4.305
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Sarkar,FH
中科院分区：
文献类型：
--
作者：
Gupta,SL;Raziuddin,A;Sarkar,FH
干扰素（IFN）作用于细胞必须首先与细胞受体相互作用。先前报道的纯化的125t标记的重组人（Hu） IFN-α2的结合和交联实验表明，IFN-α2与人细胞上的特定大分子受体结合（Joshi等，J. Biol.）。化学，257,13884-13887,1982)。基于间接证据，如神经节苷脂中和IFN制剂的抗病毒作用，以及IFN与固体载体偶联的神经节苷脂结合，各种研究者已经提出神经节苷脂可能是IFN-α/β受体的一部分。实验表明，神经节苷类可以阻断HuIFN-β的抗病毒活性，但不能阻断HuIFN-α的抗病毒活性，尽管这两种IFN都与与聚l -赖氨酸琼脂糖偶联的神经节苷类结合强烈。此外，神经节苷脂不会抑制125i标记的HuIFN-α2与人细胞特异性受体的结合，这种结合被未标记的HuIFN-α2和与神经节苷脂预孵化的HuIFN-α(Le)竞争。然而，与神经节苷类预孵育后，HuIFN-β竞争受体的能力被破坏。通过凝胶电泳鉴定ifn受体复合物的交联实验证实了这些结果。结果表明，至少在HuIFN-α物种中，神经节苷脂结合显然不在IFN分子与细胞表面受体相互作用所需的活性位点。
Interferon (IFN) action on cells must begin with an interaction with cellular receptors. Binding and cross-linking experiments reported earlier with purified125T-labeled recombinant human (Hu) IFN-α2have revealed that IFN-α2binds to a specific macromolecular receptor on human cells (Joshi et al., J. Biol. Chem. 257, 13884–13887, 1982). Based on indirect evidence such as neutralization of the antiviral action of IFN preparations by gangliosides and binding of IFNs to gangliosides coupled to solid supports, it has been suggested by various investigators that gangliosides may be a part of the IFN-α/β receptors. Experiments presented here indicate that gangliosides could block the antiviral activity of HuIFN-β, but not of HuIFN-α, although both species of IFN bound strongly to gangliosides coupled to poly-L-lysine-agarose. Furthermore, gangliosides did not inhibit the binding of125I-labeled HuIFN-α2to specific receptors on human cells, and this binding was competed out by unlabeled HuIFN-α2and HuIFN-α(Le) which were preincubated with gangliosides. However, the capacity of HuIFN-β to compete for the receptors was abolished by preincubation with gangliosides. These results were confirmed by cross-linking experiments to identify the IFN-receptor complex by gel electrophoresis. The results indicate that at least in the case of HuIFN-α species, the ganglioside binding is apparently not at the active site of the IFN molecules required for interaction with the receptors on the cell surface.