Activation of the protein tyrosine phosphatase SHP2 via the interleukin-6 signal transducing receptor protein gp130 requires tyrosine kinase Jak1 and limits acute-phase protein expression

摘要: Stimulation of the interleukin-6 (IL-6) signalling pathway occurs via IL-6 receptor-glycoprotein 130 (IL-6R-gp130) receptor complex and results in regulation acute-phase protein genes liver cells. Ligand binding to leads tyrosine phosphorylation activation Janus kinases (Jak), signal transducing subunit gp130, followed by recruitment transducer activator transcription factors STAT3 STAT1 src homology domain (SH2)-containing phosphatase (SHP2). The phosphorylated STAT dissociate from receptor, dimerize translocate nucleus where they bind enhancer sequences target genes. Phosphorylated SHP2 is able growth factor bound (grb2) thus might link Jak/STAT ras/raf/mitogen-activated kinase pathway. Here we present data on dose-dependence, kinetics requirements for after transducer, IL-6-type family complex. When human fibrosarcoma cell lines deficient Jak1, Jak2 or 2 (Tyk2) were stimulated with IL-6-soluble IL-6R complexes it was found that only Jak1-, but not Jak 2- Tyk2-deficient cells, greatly impaired. It concluded Jak1 required SHP2. This depends Tyr-759 cytoplasmatic since a Tyr-759-->Phe exchange abrogates turn elevated prolonged as well enhanced gene induction. Therefore, plays an important role regulation.