Receptors for human alpha interferon: are gangliosides involved?
Interferon (IFN) action on cells must begin with an interaction with cellular receptors. Binding and cross-linking experiments reported earlier with purified 125I-labeled recombinant human (Hu) IFN-alpha 2 have revealed that IFN-alpha 2 binds 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-alpha/beta receptors. Experiments presented here indicate that gangliosides could block the antiviral activity of HuIFN-beta, but not of HuIFN-alpha, although both species of IFN bound strongly to gangliosides coupled to poly-L-lysine-agarose. Furthermore, gangliosides did not inhibit the binding of 125I-labeled HuIFN-alpha 2 to specific receptors on human cells, and this binding was competed out by unlabeled HuIFN-alpha 2 and HuIFN-alpha(LE) which were preincubated with gangliosides. However, the capacity of HuIFN-beta 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-alpha 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.
D001665:Binding Sites; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D017471:Receptors, Interferon; D014762:Viral Interference / Q000187:drug effects
D005732:Gangliosides; D007370:Interferon Type I; D011971:Receptors, Immunologic; D017471:Receptors, Interferon