Within the IL-2R complex JAK3 phosphorylates JAK1

Stable Identifier
Reaction [transition]
Homo sapiens
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Receptor activation involves JAK1 and JAK3 as T-cells from mice lacking either kinase are unable to respond to cytokines that utilize the Common gamma chain (Rodig et al. 1998, Park et al. 1995). Naturally occurring JAK3 mutations prevent binding to the Interleukin-2 receptor, leading to severe immunodeficiency due to a lack of signaling (Macchi et al. 1995, Russell et al. 1995). Mechanistic models of receptor activation suggest that assembly of the quaternary receptor and the consequent proximity of JAK1 and JAK3, bound to the cytoplasmic domains of the beta and gamma chains, is the trigger for JAK activation (Ellery et al. 2000). JAK3 is thought to activate JAK1, as JAK3 does not require tyrosine phosphorylation to activate its kinase activity (Liu et al. 1997), and JAK3 has been demonstrated to phosphorylate JAK1 in response to IL-2 (Kawahara et al. 1995). JAK3 also becomes phosphorylated in response to IL-2 (Johnston et al. 1994), either by JAK1 trans-activation or by an indirect mechanism. The activated JAKs then phosphorylate critical tyrosine residues within IL2RB.

Literature References
PubMed ID Title Journal Year
8022485 Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2

Ortaldo, JR, Shibuya, K, Blake, TB, McVicar, DW, Kawamura, M, Chen, YQ, Johnston, JA, O'Shea, JJ, Kirken, RA

Nature 1994
10825200 Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2) signaling: activation of syk depends on Jak3; however, neither Syk nor Lck is required for IL-2-mediated STAT activation

Changelian, PS, Cheng, TP, Frucht, DM, Candotti, F, Zhou, YJ, Geahlen, RL, Galon, J, Magnuson, KS, Gadina, M, O'Shea, JJ

Mol Cell Biol 2000
Catalyst Activity

protein tyrosine kinase activity of IL2:IL2R trimer:JAK1:JAK3 [plasma membrane]

Orthologous Events
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