Differences in interferon alpha and beta signaling. Interferon beta selectively induces the interaction of the alpha and betaL subunits of the type I interferon receptor.
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.
Platanias
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LC
Section of Hematology-Oncology, Department of Medicine, University of Illinois at Chicago, 60607, USA.
Uddin
S
S
Domanski
P
P
Colamonici
O R
OR
D000818:Animals; D006801:Humans; D016898:Interferon-alpha / Q000502:physiology*; D016899:Interferon-beta / Q000502:physiology*; D007700:Kinetics; D007739:L Cells; D046911:Macromolecular Substances; D008565:Membrane Proteins; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D011233:Precipitin Tests; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000502:physiology*; D011994:Recombinant Proteins; D015398:Signal Transduction
D016898:Interferon-alpha; D046911:Macromolecular Substances; D008565:Membrane Proteins; D010750:Phosphoproteins; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D053633:Receptor, Interferon alpha-beta; D019000:Phosphotyrosine; D016899:Interferon-beta