Adaptor Proteins, Signal Transducing; Peptides; Promoter Regions (Genetics); Proteins; Rats; Receptors, Cytokine; Receptors, Oncostatin M; Signal Transduction; Tyrosine; Oncostatin M; Mitogen-Activated Protein Kinases; Lymphokines; Adaptor Proteins, Vesicular Transport; Animals; COS Cells; Dimerization; GRB2 Adaptor Protein; Growth Inhibitors; Interleukin-6; Leukemia Inhibitory Factor; alpha-Macroglobulins
Abstract :
[en] The common use of the cytokine receptor gp130 has served as an explanation for the extremely redundant biological activities exerted by interleukin (IL)-6-type cytokines. Indeed, hardly any differences in signal transduction initiated by these cytokines are known. In the present study, we demonstrate that oncostatin M (OSM), but not IL-6 or leukemia inhibitory factor, induces tyrosine phosphorylation of the Shc isoforms p52 and p66 and their association with Grb2. Concomitantly, OSM turns out to be a stronger activator of ERK1/2 MAPKs. Shc is recruited to the OSM receptor (OSMR), but not to gp130. Binding involves Tyr(861) of the OSMR, located within a consensus binding sequence for the Shc PTB domain. Moreover, Tyr(861) is essential for activation of ERK1/2 and for full activation of the alpha(2)-macroglobulin promoter, but not for an exclusively STAT-responsive promoter. This study therefore provides evidence for qualitative differential signaling mechanisms exerted by IL-6-type cytokines.
Disciplines :
Biochemistry, biophysics & molecular biology
Identifiers :
UNILU:UL-ARTICLE-2008-730
Author, co-author :
Hermanns, H. M.
Radtke, S.
Schaper, F.
Heinrich, P. C.
Behrmann, Iris ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Language :
English
Title :
Non-redundant signal transduction of interleukin-6-type cytokines. The adapter protein Shc is specifically recruited to rhe oncostatin M receptor
Publication date :
2001
Journal title :
Journal of Biological Chemistry
ISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland