IL-4 FUNCTION CAN BE TRANSFERRED TO THE IL-2 RECEPTOR BY TYROSINE-CONTAINING SEQUENCES FOUND IN THE IL-4 RECEPTOR-ALPHA CHAIN

IL-4 binds to a cell surface receptor complex that consists of the IL- 4-binding protein (IL-4R alpha) and the gamma chain of the IL-2 recept or complex (gamma c). The receptors for IL-4 and IL-2 have several fea tures in common; both use the gamma c as a receptor component, and bot h activate the Janus kinases JAK-1 and JAK-3. In spite of these simila rities, IL-4 evokes specific responses, including the tyrosine phospho rylation of 4PS/IRS-2 and the induction of CD23. To determine whether sequences within the cytoplasmic domain of the IL-4R alpha specify the se IL-4-specific responses, we transplanted the insulin IL-4 receptor motif (14R motif) of the huIL-4R alpha to the cytoplasmic domain of a truncated IL-2R beta. In addition, we transplanted a region that conta ins peptide sequences shown to block State binding to DNA. We analyzed the ability of cells expressing these IL-2R-IL-4R chimeric constructs to respond to IL-2. We found that IL-4 function could be transplanted to the IL-2 receptor by these regions and that proliferative and diff erentiative functions can be induced by different receptor sequences.