Interferon-beta interrupts interleukin-6-dependent signaling events in myeloma cells.
Type I interferons (IFNs-alpha and IFN-beta) bind to a common receptor to exert strong antiproliferative activity on a broad range of cell types, including interleukin-6 (IL-6)-dependent myeloma cells. In this study, we investigated the effect of IFN-beta pretreatment on IL-6-stimulated mitogenic signaling in the human myeloma cell line U266. IL-6 induced transient tyrosine phosphorylation of the IL-6-receptor signal-transducing subunit gp130, the gp130-associated protein tyrosine kinases Jak1,Jak2, and Tyk2, the phosphotyrosine phosphatase PTP1D/Syp, the adaptor protein Shc and the mitogen-activated protein kinase Erk2, and accumulation of GTP-bound p21ras. Prior treatment of U266 cells with IFN-beta downregulated IL-6- induced tyrosine phosphorylation of gp130, Jak2, PTP1D/Syp, Shc, and Erk2, and GTP-loading of p21ras. Further analysis indicated that treatment with IFN-beta disrupted IL-6- induced binding of PTP1D/Syp to gp130 and the adaptor protein Grb2; IFN-beta pretreatment also interfered with IL-6- induced interaction of Shc with Grb2 and a 145-kD tyrosine-phosphorylated protein. These results suggest a novel mechanism whereby type I IFNs interrupt IL-6- promoted mitogenesis of myeloma cells in part by preventing the formation of essential signaling complexes leading to p21ras activation.[1]References
- Interferon-beta interrupts interleukin-6-dependent signaling events in myeloma cells. Berger, L.C., Hawley, R.G. Blood (1997) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
