Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Adaptor Proteins, Vesicular Transport*
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Animals
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COS Cells
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Dimerization
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GRB2 Adaptor Protein
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Growth Inhibitors / pharmacology
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Interleukin-6 / pharmacology*
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Leukemia Inhibitory Factor
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Lymphokines / pharmacology
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Mitogen-Activated Protein Kinases / metabolism
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Oncostatin M
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Peptides / pharmacology
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Promoter Regions, Genetic
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Proteins / metabolism*
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Rats
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Receptors, Cytokine / chemistry
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Receptors, Cytokine / metabolism*
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Receptors, Oncostatin M
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Shc Signaling Adaptor Proteins
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Signal Transduction*
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Tyrosine / physiology
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alpha-Macroglobulins / genetics
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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GRB2 Adaptor Protein
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Grb2 protein, rat
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Growth Inhibitors
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Interleukin-6
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Leukemia Inhibitory Factor
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Lymphokines
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Peptides
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Proteins
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Receptors, Cytokine
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Receptors, Oncostatin M
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Shc Signaling Adaptor Proteins
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Shc1 protein, rat
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Src Homology 2 Domain-Containing, Transforming Protein 1
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alpha-Macroglobulins
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Oncostatin M
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Tyrosine
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Mitogen-Activated Protein Kinases