FUNCTIONAL ACTIVATION OF JAK1 AND JAK3 BY SELECTIVE ASSOCIATION WITH IL-2 RECEPTOR SUBUNITS

The interleukin-2 receptor (IL-2) consists of three subunits: the IL-2 R alpha, IL-2R beta, and IL-2R gamma 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 kina ses Jak1 and Jak3. Jak1 and Jak3 were found to be selectively associat ed with the ''serine-rich'' region of IL-2R beta and the carboxyl-term inal region of IL-2R gamma, 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 exp ression of Jak3 complementary DNA. Thus, activation of Jak1 and Jak3 m ay be a key event in IL-2 signaling.