| Autor: |
Platanias, Leonidas C., Uddin, Shahab, Yetter, Andrew, Sun, Xiao-Jian, White, Morris F. |
| Zdroj: |
Journal of Biological Chemistry; January 1996, Vol. 271 Issue: 1 p278-282, 5p |
| Abstrakt: |
Binding of interferon α (IFNα) to its receptor induces activation of the Tyk-2 and Jak-1 tyrosine kinases and tyrosine phosphorylation of multiple downstream signaling elements, including the Stat components of the interferon-stimulated gene factor 3 (ISGF-3). IFNα also induces tyrosine phosphorylation of IRS-1, the principle substrate of the insulin receptor. In this study we demonstrate that various Type I IFNs rapidly stimulate tyrosine phosphorylation of IRS-2. This is significant since IRS-2 is the major IRS protein found in hematopoietic cells. The IFNα-induced phosphorylated form of IRS-2 associates with the p85 regulatory subunit of the phosphatidylinositol 3′-kinase, suggesting that this kinase participates in an IFNα-signaling cascade downstream of IRS-2. We also provide evidence for an interaction of IRS-2 with Tyk-2, suggesting that Tyk-2 is the kinase that phosphorylates this protein during IFNα stimulation. A conserved region in the pleckstrin homology domain of IRS-2 may be required for the interaction of IRS-2 with Tyk-2, as shown by the selective binding of glutathione S-transferase (GST) fusion proteins containing the IRS-2-IH1PHor IRS-1-IH1PHdomains to Tyk-2 but not other Janus kinases in vitro. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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