FEBS Letters | |
Differential inhibition of IL‐6‐type cytokine‐induced STAT activation by PMA | |
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
【 预 览 】
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