Koettnitz K, Kalthoff F S
Sandoz Research Institute, Vienna, Austria.
Eur J Immunol. 1993 Apr;23(4):988-91. doi: 10.1002/eji.1830230437.
The signaling pathway used by the murine or human interleukin-4 receptor (hIL-4R) has not been elucidated so far. As an approach to mapping the cytoplasmic regions of the hIL-4R that are essential for mediating the biological response upon IL-4 binding we have cloned and expressed the wild-type hIL-4R and several cytoplasmic deletion mutants in the murine IL-3-dependent pro-B cell line BA/F3. Transfection of the wild-type hIL-4R conferred the ability on BA/F3 cells to proliferate in a dose-dependent way when treated with human IL-4. The analysis of six deletion mutants indicated that the signaling function of the hIL-4R depends on sequences within two discontinuous regions that are located between amino acid IIe233 and Ser365 and Thr462 and Ala580 of the intracytoplasmic domain. The deletion of either of these regions totally abrogated IL-4-inducible growth. The relevance of our data is discussed in relation to the results obtained from similar studies with other members of the hematopoietin receptor superfamily.
迄今为止，小鼠或人白细胞介素-4受体（hIL-4R）所使用的信号通路尚未阐明。作为一种确定hIL-4R胞质区域的方法，这些区域对于介导IL-4结合后的生物学反应至关重要，我们已在小鼠IL-3依赖的前B细胞系BA/F3中克隆并表达了野生型hIL-4R和几个胞质缺失突变体。当用人类IL-4处理时，野生型hIL-4R的转染赋予了BA/F3细胞以剂量依赖性方式增殖的能力。对六个缺失突变体的分析表明，hIL-4R的信号功能取决于位于胞质结构域氨基酸Ile233和Ser365以及Thr462和Ala580之间的两个不连续区域内的序列。这些区域中的任何一个缺失都会完全消除IL-4诱导的生长。我们将结合从造血受体超家族其他成员的类似研究中获得的结果来讨论我们数据的相关性。
