Science · 1994 · 594 citations · 28 references
Life SciencesImmunologyMolecular BiologyCell SignalingMolecular ImmunologySignal TransductionCell Signaling NetworksCytokine BiologyCytokine Receptor SignalingCytokine RegulationCytokine SignalingImmune SignalingActivationCytokine Receptor Signaling ComplexesInterleukin Receptor SignalingJak-stat Signaling PathwayJanus Kinase-stat Signaling ActivationProtein Tyrosine PhosphorylationTyrosine Phosphorylation Signaling
The IL‑2 receptor is composed of α, β, and γ subunits, with the γ chain shared by IL‑4, IL‑7, and IL‑9 receptors, and IL‑2 stimulation triggers phosphorylation and activation of the Janus kinases Jak1 and Jak3. Jak1 binds the serine‑rich region of IL‑2Rβ while Jak3 associates with the carboxyl‑terminal region of IL‑2Rγ, and both interactions are essential for IL‑2 signaling, as shown by restored responsiveness in Jak3‑deficient fibroblasts upon Jak3 expression, indicating that Jak1 and Jak3 activation is a key event in IL‑2 signaling.
The interleukin-2 receptor (IL-2R) consists of three subunits: the IL-2Rα, IL-2Rβ, and IL-2Rγ chains, the last of which is also used in the receptors for IL-4, IL-7, and IL-9. Stimulation with IL-2 induces the tyrosine phosphorylation and activation of the Janus kinases Jak1 and Jak3. Jak1 and Jak3 were found to be selectively associated with the "serine-rich" region of IL-2Rβ and the carboxyl-terminal region of IL-2Rγ, respectively. Both regions were necessary for IL-2 signaling. Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. Thus, activation of Jak1 and Jak3 may be a key event in IL-2 signaling.
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Interleukin-2 Receptor γ Chain: a Functional Component of the Interleukin-7 Receptor
Masayuki Noguchi, Yoshiaki Nakamura, Sarah M. Russell et al. · Science · 1993 · 1.1K citations · Full text