The murine IL-13 receptor alpha 2: molecular cloning, characterization, and comparison with murine IL-13 receptor alpha 1.
The murine IL-13 receptor alpha 2: molecular cloning, characterization, and comparison with murine IL-13 receptor alpha 1.
复制标题
DOI：
--
复制
发表时间：
1998-09
影响因子：
4.4
通讯作者：
Debra D. Donaldson;M. Whitters;Lori Fitz;T. Neben;H. Finnerty;Sheryl L. Henderson;R. O'hara;David R. Beier;Katherine Turner;Clive Wood;Mary Collins
中科院分区：
文献类型：
--
作者：
Debra D. Donaldson;M. Whitters;Lori Fitz;T. Neben;H. Finnerty;Sheryl L. Henderson;R. O'hara;David R. Beier;Katherine Turner;Clive Wood;Mary Collins
IL-13受体复合物的两种组分IL-4 R和低亲和力IL-13结合链IL-13 R α 1已在小鼠和人中克隆。已经在人类中描述了IL-13的另外的高亲和力结合链，IL-13 R α 2。我们从胸腺中分离出编码人IL-13 R α 2的小鼠直系同源物的cDNA。鼠IL-13 R α 2（mIL-13 R α 2）的预测蛋白质序列与人IL-13 R α 2具有59%的总体同一性，并且与鼠低亲和力IL-13结合亚基IL-13 R α 1密切相关。两条mIL-13结合链的基因均定位于X染色体。使用BIACORE仪器通过表面等离子体共振证明mIL-13 R α 2.Fc蛋白和IL-13之间的特异性相互作用。用mIL-13 R α 2转染的Ba/F3细胞表达5000个分子/细胞，并以0.5至1.2 nM的单个Kd结合IL-13。然而，这些细胞对IL-13没有应答增殖，并且IL-4剂量反应不受高浓度IL-13的影响。相反，Ba/F3细胞表达mIL-13 R α 1导致对IL-13的敏感增殖反应。与其对IL-13的较低亲和力一致，IL-13 R α 1.Fc在体外中和IL-13方面的有效性比IL-13 R α 2.Fc低100倍。这些结果表明，mIL-13 R α 2和mIL-13 R α 1在功能上不等同，并预测了每种多肽在IL-13 R复合物形成和IL-13信号转导调节中的不同作用。
Two components of a receptor complex for IL-13, the IL-4R and a low affinity IL-13-binding chain, IL-13R alpha 1, have been cloned in mice and humans. An additional high affinity binding chain for IL-13, IL-13R alpha 2, has been described in humans. We isolated a cDNA from the thymus that encodes the murine orthologue of the human IL-13R alpha 2. The predicted protein sequence of murine IL-13R alpha 2 (mIL-13R alpha 2) has 59% overall identity to human IL-13R alpha 2 and is closely related to the murine low affinity IL-13-binding subunit, IL-13R alpha 1. The genes for both mIL-13-binding chains map to the X chromosome. A specific interaction between mIL-13R alpha 2.Fc protein and IL-13 was demonstrated by surface plasmon resonance using a BIACORE instrument. Ba/F3 cells that were transfected with mIL-13R alpha 2 expressed 5000 molecules per cell and bound IL-13 with a single Kd of 0.5 to 1.2 nM. However, these cells did not proliferate in response to IL-13, and the IL-4 dose response was unaffected by high concentrations of IL-13. In contrast, the expression of mIL-13R alpha 1 by Ba/F3 cells resulted in a sensitive proliferative response to IL-13. Consistent with its lower affinity for IL-13, IL-13R alpha 1.Fc was 100-fold less effective than IL-13R alpha 2.Fc in neutralizing IL-13 in vitro. These results show that mIL-13R alpha 2 and mIL-13R alpha 1 are not functionally equivalent and predict distinct roles for each polypeptide in IL-13R complex formation and in the modulation of IL-13 signal transduction.