Reactome | Activation of JAK kinases

Activation of JAK kinases

Stable Identifier

R-HSA-909729

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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The two chains IFNAR1 and IFNAR2 are pre-associated with the JAK kinases TYK2 and JAK1, respectively. Receptor heterodimerization brings these JAK kinases into close proximity and they are activated by reciprocal trans-phosphorylation. Tyr-1054 and Tyr-1055 within the activation loop of TYK2 sub-domain VII are critical for TYK2 activation. For JAK1 two tyrosine residues with in the KEYY motif (Tyr 1034 and Tyr 1035) of the kinase domain are thought to be transphosphorylated.

Literature References

PubMed ID	Title	Journal	Year
9334213	A region of the beta subunit of the interferon alpha receptor different from box 1 interacts with Jak1 and is sufficient to activate the Jak-Stat pathway and induce an antiviral state Domanski, P, Fish, E, Nadeau, OW, Witte, M, Platanias, LC, Yan, H, Krolewski, J, Pitha, P, Colamonici, OR	J Biol Chem	1997
8702790	Interferon-alpha-dependent activation of Tyk2 requires phosphorylation of positive regulatory tyrosines by another kinase Gauzzi, MC, Velazquez, L, McKendry, R, Mogensen, KE, Fellous, M, Pellegrini, S	J Biol Chem	1996