Reference : Differential inhibition of IL-6-type cytokine-induced STAT activation by PMA
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Differential inhibition of IL-6-type cytokine-induced STAT activation by PMA
Terstegen, L. [> >]
Maassen, B. G. [> >]
Radtke, S. [> >]
Behrmann, Iris mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Schaper, F. [> >]
Heinrich, P. C. [> >]
Graeve, L. [> >]
Gatsios, P. [> >]
FEBS Letters
Elsevier Science
Yes (verified by ORBilu)
The Netherlands
[en] Transfection ; Receptors, Interleukin ; Receptors, Cytokine ; Proteins ; Protein-Tyrosine Kinases ; Protein Tyrosine Phosphatases ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Peptides ; Receptors, Interleukin-5 ; Receptors, OSM-LIF ; Receptors, Oncostatin M ; Transcription Factors ; Trans-Activators ; Tetradecanoylphorbol Acetate ; Suppressor of Cytokine Signaling Proteins ; STAT3 Transcription Factor ; STAT1 Transcription Factor ; Repressor Proteins ; Recombinant Fusion Proteins ; Oncostatin M ; Mitogen-Activated Protein Kinases ; Enzyme Activation ; Dimerization ; DNA-Binding Proteins ; Cytokine Receptor gp130 ; Cell Line ; Binding Sites ; Antigens, CD ; Animals ; Growth Inhibitors ; Humans ; Interleukin-5 ; Membrane Glycoproteins ; MAP Kinase Signaling System ; Lymphokines ; Leukemia Inhibitory Factor Receptor alpha Subunit ; Leukemia Inhibitory Factor ; Janus Kinase 1 ; Intracellular Signaling Peptides and Proteins ; Interleukin-6 ; Amino Acid Motifs
[en] 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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