Jj. Ryan et al., CHARACTERIZATION OF A MOBILE STAT6 ACTIVATION MOTIF IN THE HUMAN IL-4RECEPTOR, The Journal of immunology (1950), 161(4), 1998, pp. 1811-1821
The IL-4R induces proliferation and gene expression through the use of
conserved tyrosine residues located in growth and gene regulation dom
ains, respectively. We demonstrate that residues surrounding these con
served tyrosines (juxtatyrosine residues) are essential for the proper
activation of the signaling molecules IRS-2 and Stat6, as well as for
IL-4-induced gene expression. Further, we found that the IL-4R gene r
egulation domain (amino acids 557-657) contains a tyrosine-based seque
nce (EAGYKAF) that can convey Stat6 DNA binding and gene expression ac
tivities to a minimally active IL-4R mutant, Delta 557. Thus, this tyr
osine-based sequence can function as a mobile Stat6 activation cassett
e. However, mutants bearing this sequence induced CD23 expression much
less efficiently than did wild-type IL-4R, requiring 150-fold more IL
-4 to reach maximal CD23 expression. Our results indicate the importan
ce of juxtatyrosine residues in IL-4R signaling and argue for an essen
tial role of extended domain structure in the recognition and function
of juxtatyrosine sequences.