Tyrosine phosphorylation of the alpha and beta subunits of the type I interferon receptor. Interferon-beta selectively induces tyrosine phosphorylation of an alpha subunit-associated protein

• Published in: The Journal of biological chemistry Vol. 269; no. 27; pp. 17761 - 17764
• Main Authors: PLATANIAS, L. C, UDDIN, S, COLAMONICI, O. R
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 08.07.1994
• Subjects: Biological and medical sciences; Cell physiology; Fundamental and applied biological sciences. Psychology; Humans; Interferon-alpha - metabolism; Interferon-beta - metabolism; Molecular and cellular biology; Phosphorylation; Proteins - metabolism; Receptors, Interferon - chemistry; Receptors, Interferon - metabolism; Signal Transduction; Tumor Cells, Cultured; Tyrosine - metabolism; Human; Signal transduction; Membrane receptor; Immunoprecipitation reaction; Enzyme; Transferases; Cytokine; Immunoblotting assay; Interferon; Acute lymphocytic leukemia; Subunit; Protein-tyrosine kinase
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(17)32371-2

We studied the phosphorylation of the alpha and beta subunits of the Type I interferon (IFN) receptor induced by Type I IFNs in the human U-266 and MOLT-4 cell lines. Both IFN-alpha and IFN-beta induced tyrosine phosphorylation of the beta subunit of the receptor. The Type I IFN-induced tyrosine phosphorylation of the beta subunit was rapid and transient, being detectable within 1 min of Type I IFN treatment and gradually diminishing to almost base-line levels by 60 min. All Type I IFNs studied were found to induce tyrosine phosphorylation of the alpha subunit of the Type I IFN receptor, the p135tyk2 and JAK-1 tyrosine kinases, and the ISGF3 alpha components. Interestingly, IFN-beta, but not IFN-alpha or IFN-omega, induced tyrosine phosphorylation of an alpha subunit-associated protein with an apparent molecular mass of approximately 100 kDa (p100). These data suggest the existence of a common signaling pathway(s) for Type I IFNs involving the alpha and beta subunits of the receptor, the tyrosine kinases p135tyk2 and JAK-1, and the ISGF3 alpha components. However, differences between the signaling pathways of different Type I IFNs exist, as suggested by tyrosine phosphorylation of an alpha subunit-associated protein only in response to IFN-beta.