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  • Title: Differential inhibition of IL-6-type cytokine-induced STAT activation by PMA.
    Author: Terstegen L, Maassen BG, Radtke S, Behrmann I, Schaper F, Heinrich PC, Graeve L, Gatsios P.
    Journal: FEBS Lett; 2000 Jul 28; 478(1-2):100-4. PubMed ID: 10922477.
    Abstract:
    Prior activation of mitogen-activated protein kinases by phorbol 13-myristate 12-acetate (PMA) results in an inhibition of interleukin (IL)-6-induced activation of the Janus kinase/signal transducer and activator of transcription (STAT) signaling pathway which is most likely mediated by the induction of suppressor of cytokine signaling-3 and requires the specific SHP2 binding site Y759 of the IL-6 signal transducer gp130. In this study, we demonstrate that PMA inhibits STAT activation by IL-6 and the related cytokine leukemia inhibitory factor (LIF) but not by oncostatin M (OSM). Since the LIF receptor also contains an SHP2 recruitment site whereas the OSM receptor lacks such a module, we propose that two SHP2 binding modules within a homo- or heterodimeric receptor are necessary to mediate the PMA inhibitory effect.
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