Ryan J J, McReynolds L J, Huang H, Nelms K, Paul W E
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
J Immunol. 1998 Aug 15;161(4):1811-21.
The IL-4R induces proliferation and gene expression through the use of conserved tyrosine residues located in growth and gene regulation domains, respectively. We demonstrate that residues surrounding these conserved 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 regulation domain (amino acids 557-657) contains a tyrosine-based sequence (EAGYKAF) that can convey Stat6 DNA binding and gene expression activities to a minimally active IL-4R mutant, delta 557. Thus, this tyrosine-based sequence can function as a mobile Stat6 activation cassette. 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 importance of juxtatyrosine residues in IL-4R signaling and argue for an essential role of extended domain structure in the recognition and function of juxtatyrosine sequences.
IL-4R分别通过位于生长和基因调控结构域的保守酪氨酸残基来诱导细胞增殖和基因表达。我们证明，这些保守酪氨酸周围的残基（毗邻酪氨酸残基）对于信号分子IRS-2和Stat6的正常激活以及IL-4诱导的基因表达至关重要。此外，我们发现IL-4R基因调控结构域（氨基酸557 - 657）包含一个基于酪氨酸的序列（EAGYKAF），该序列可将Stat6 DNA结合和基因表达活性传递给活性最低的IL-4R突变体delta 557。因此，这个基于酪氨酸的序列可作为一个可移动的Stat6激活盒发挥作用。然而，携带该序列的突变体诱导CD23表达的效率远低于野生型IL-4R，达到最大CD23表达所需的IL-4量要多150倍。我们的结果表明毗邻酪氨酸残基在IL-4R信号传导中的重要性，并证明扩展结构域结构在毗邻酪氨酸序列的识别和功能中起关键作用。
