|
|
 Previous Article | Table of Contents | Next Article 
Interferon-beta interrupts interleukin-6-dependent signaling events in
myeloma cells
LC Berger and RG Hawley
Division of Cancer Biology, Sunnybrook Health Science Centre, Toronto,
Canada.
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.
Volume 89,
Issue 1,
pp. 261-271,
01/01/1997
Copyright © 1997 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
O. Hjertner, H. Hjorth-Hansen, M. Borset, C. Seidel, A. Waage, and A. Sundan
Bone morphogenetic protein-4 inhibits proliferation and induces apoptosis of multiple myeloma cells
Blood,
January 15, 2001;
97(2):
516 - 522.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Wang, Y. Miyakawa, N. Fox, and K. Kaushansky
Interferon-alpha directly represses megakaryopoiesis by inhibiting thrombopoietin-induced signaling through induction of SOCS-1
Blood,
September 15, 2000;
96(6):
2093 - 2099.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. E. Plowright, Z. Li, P. L. Bergsagel, M. Chesi, D. L. Barber, D. R. Branch, R. G. Hawley, and A. K. Stewart
Ectopic expression of fibroblast growth factor receptor 3 promotes myeloma cell proliferation and prevents apoptosis
Blood,
February 1, 2000;
95(3):
992 - 998.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ferlin-Bezombes, M. Jourdan, J. Liautard, J. Brochier, J.-F. Rossi, and B. Klein
IFN-{alpha} Is a Survival Factor for Human Myeloma Cells and Reduces Dexamethasone-Induced Apoptosis
J. Immunol.,
September 15, 1998;
161(6):
2692 - 2699.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kim, T. S. Hawley, R. G. Hawley, and H. Baumann
Protein Tyrosine Phosphatase 2 (SHP-2) Moderates Signaling by gp130 but Is Not Required for the Induction of Acute-Phase Plasma Protein Genes in Hepatic Cells
Mol. Cell. Biol.,
March 1, 1998;
18(3):
1525 - 1533.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Hallek, P. Leif Bergsagel, and K. C. Anderson
Multiple Myeloma: Increasing Evidence for a Multistep Transformation Process
Blood,
January 1, 1998;
91(1):
3 - 21.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Hermanns, S. Radtke, F. Schaper, P. C. Heinrich, and I. Behrmann
Non-redundant Signal Transduction of Interleukin-6-type Cytokines. THE ADAPTER PROTEIN Shc IS SPECIFICALLY RECRUITED TO THE ONCOSTATIN M RECEPTOR
J. Biol. Chem.,
December 22, 2000;
275(52):
40742 - 40748.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
