Interferon-beta interrupts interleukin-6-dependent signaling events in myeloma cells.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Berger LC,Hawley RG

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

261-71

issue

1

eissn

0006-4971

issn

1528-0020

journal_volume

89

pub_type

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