Interleukin-6 (IL6) activates the tyrosine phosphorylation of STATs (Akira et al. 1994, Zhong et al. 1994) by receptor-associated JAKs (Hemmann et al. 1996) at a site that is essential for dimerization. For STAT1 this is tyrosine-701, for STAT3 tyrosine-705 (Kaptein et al. 1996, Shuai et al. 1994). Tyrosine phosphorylation leads to homo- or heterodimerization and translocation to the nucleus (Zhong et al. 1994), where the dimers bind to enhancers of IL6- inducible genes e.g. acute phase protein genes, resulting in transcriptional activation.
Heinrich, PC, Sasse, J, Horn, F, Darnell JE, Jr, Zhong, Z, Graeve, L, Hemmann, U, Wollmer, A, Kurapkat, G, Heesel, B, Grötzinger, J, Gerhartz, C
non-membrane spanning protein tyrosine kinase activity of Tyrosine phosphorylated IL6 receptor hexamer:Activated JAKs:STAT1,STAT3 [plasma membrane]
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