Identification of the critical portions of the human IL-4 receptor alpha chain for activation of STAT6.

Interleukin-4 (IL-4) has been shown to activate Janus kinase (Jak)-1 and Jak-3, followed by activation of STAT (signal transducers and activators of transcription) 6. This Jak-STAT pathway is central to the initiation of IL-4 activities. In this study, we identified the essential region for the proliferation signal and activation of Jak-1, Jak-3, and STAT6 in the cytoplasmic domain of the human IL-4 receptor alpha chain (hIL-4R alpha) using a mouse T cell line CTLL-2. We found that the region between amino acid 353 and 393 is critical for the proliferation signal and activation of STAT6, but not for tyrosine phosphorylation of Jaks. These results suggest that in addition to the "Box-1" portion, which is known to be essential for Jak-1 activation, the more membrane-distal region of hIL-4R alpha is also necessary for activation of STAT6.