Functional Activation of Jak1 and Jak3 by Selective Association with IL-2 Receptor Subunits

TLDR

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.

Abstract

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.