Human interleukin-4 receptor signaling requires sequences contained within two cytoplasmic regions.

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.