Interferon-b Interrupts Interleukin-6 – Dependent Signaling Events in Myeloma Cells

Type I interferons (IFNs-a and IFN-b) bind to a common redownregulated IL-6–induced tyrosine phosphorylation of gp130, Jak2, PTP1D/Syp, Shc, and Erk2, and GTP-loading of ceptor to exert strong antiproliferative activity on a broad range of cell types, including interleukin-6 (IL-6)–dependent p21. Further analysis indicated that treatment with IFN-b disrupted IL-6–induced binding of PTP1D/Syp to gp130 and myeloma cells. In this study, we investigated the effect of IFN-b pretreatment on IL-6–stimulated mitogenic signaling the adaptor protein Grb2; IFN-b pretreatment also interfered with IL-6–induced interaction of Shc with Grb2 and a 145in the human myeloma cell line U266. IL-6 induced transient tyrosine phosphorylation of the IL-6 receptor signal-transkD tyrosine-phosphorylated protein. These results suggest a novel mechanism whereby type I IFNs interrupt IL-6–producing subunit gp130, the gp130-associated protein tyrosine kinases Jak1, Jak2, and Tyk2, the phosphotyrosine phosphamoted mitogenesis of myeloma cells in part by preventing the formation of essential signaling complexes leading to tase PTP1D/Syp, the adaptor protein Shc and the mitogenactivated protein kinase Erk2, and accumulation of GTPp21 activation. q 1997 by The American Society of Hematology. bound p21. Prior treatment of U266 cells with IFN-b