Non-redundant signal transduction of interleukin-6-type cytokines - The adapter protein Shc is specifically recruited to the oncostatin M receptor

The common use of the cytokine receptor gp130 has served as an explanation for the extremely redundant biological activities exerted by interleukin (I L)-6-type cytokines.Indeed, hardly any differences in signal transduction i nitiated by these cytokines are known. In the present study, we demonstrate that oncostatin M (OSM), but not IL-6 or leukemia inhibitory factor, induc es tyrosine phosphorylation of the Shc isoforms p52 and p66 and their assoc iation with Grb2. Concomitantly, OSM turns out to be a stronger activator o f ERK1/2 MAPKs, Shc is recruited to the OSM receptor (OSMR), but not to gp1 30. Binding involves Tyr(816) Of the OSMR, located within a consensus bindi ng sequence for the Shc PTB domain. Moreover, Tyr(861) is essential for act ivation of ERK1/2 and for full activation of the alpha (2)-macroglobulin pr omoter, but not for an exclusively STAT-responsive promoter. This study the refore provides evidence for qualitative differential signaling mechanisms exerted by IL-6-type cytokines.