Differential inhibition of IL‐6‐type cytokine‐induced STAT activation by PMA

FEBS Letters

Schaper, Fred¹  Radtke, Simone¹  Behrmann, Iris¹  Gatsios, Petros¹  Heinrich, Peter C.¹  Maassen, Björn G.¹  Terstegen, Lara¹  Graeve, Lutz¹ 

[1] Institut für Biochemie, Klinikum der RWTH Aachen, Pauwelsstr. 30, 52057 Aachen, Germany

关键词: Cytokine signaling;    Cross-talk;    Mitogen-activated protein kinase;    Signal transducer and activator of transcription;    Suppressor of cytokine signaling;    DMEM;    Dulbecco's modified Eagle's medium;    EMSA;    electrophoretic mobility shift assay;    IL;    interleukin;    Jak;    Janus kinase;    LIF;    leukemia inhibitory factor;    MAP;    mitogen-activated protein;    OSM;    oncostatin M;    PMA;    phorbol 13-myristate 12-acetate;    SH2;    Src homology 2;    STAT;    signal transducer and activator of transcription;    SOCS;    suppressor of cytokine signaling;   

DOI  :  10.1016/S0014-5793(00)01826-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown