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Differential inhibition of IL‐6‐type cytokine‐induced STAT activation by PMA
Author(s) -
Terstegen Lara,
Maassen Björn G.,
Radtke Simone,
Behrmann Iris,
Schaper Fred,
Heinrich Peter C.,
Graeve Lutz,
Gatsios Petros
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01826-3
Subject(s) - oncostatin m , glycoprotein 130 , leukemia inhibitory factor , stat protein , leukemia inhibitory factor receptor , janus kinase , jak stat signaling pathway , suppressor of cytokine signaling 1 , chemistry , microbiology and biotechnology , socs3 , stat , stat3 , signal transduction , cytokine receptor , cytokine , janus kinase 1 , interleukin 6 , biology , biochemistry , tyrosine kinase , immunology , suppressor , gene
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.