JAK1,JAK2,(TYK2) bind IL6ST

Stable Identifier
R-HSA-1067646
Type
Reaction
Species
Homo sapiens
Compartment
Synonyms
JAKs associate with IL6ST (gp130)
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The tyrosine kinases JAK1, JAK2 and Tyk2 associate with the cytoplasmic domain of the interleukin-6 receptor beta subunit (IL6ST, GP130) (Stahl et al. 1994), via interactions with the membrane proximal Box1/Box2 region, motifs conserved amongst many cytokine receptors. This region of IL6ST is sufficient for JAK activation (Narazaki et al. 1994). The interbox region is also involved in JAK binding (Haan et al. 2000). This is a strong and stable assocation considered to be constitutive (Heinrich et al. 2003). The N-terminal region of JAK1 contains a FERM domain that is crucial for receptor association (Haan et al. 2001, Hilkens et al. 2001). Interleukin-6 (IL6) induces rapid phosphorylation and activation of JAK1, JAK2 and TYK2 in cells (Guschin et al. 1995), but experiments in JAK1 deficient cell lines (Guschin et al. 1995) and Jak1 -/- mice (Rodig et al. 1998) where IL6-induced responses (Il6st phosphorylation and actvation of Stat1 and Stat3) were greatly impaired, suggest that JAK1 is the key kinase for signal transduction. One possible model is that JAK1 associates with IL6ST and triggers downstream events, but requires either JAK2 or TYK2 for efficient activation or ligand-induced dimerization of the receptor complex.

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