Interaction of the c-fes proto-oncogene product with the interleukin-4 receptor

Interleukin-4 (IL-4) regulates proliferation and differentiation of a variety of hematopoietic cell lineages through binding to the IL-4 receptor (IL-4R). Recently, we have demonstrated that IL-4 induces tyrosine phosphorylation of several proteins including the IL-4R and also induces association of phosphatidylinositol-3 kinase with the IL-4R. Since IL-4 induces tyrosine phosphorylation, we speculated that some tyrosine kinase may associate with the IL-4R. In this study, we demonstrate that IL-4 induces tyrosine phosphorylation of a protein closely related to, or identical to the c-fes protooncogene-encoded protein tyrosine kinase (FES). Furthermore, tyrosine phosphorylated FES or the closely related protein is found associated with the IL-4R. We also demonstrate that FES associates with the IL-4R in COS7 cells transfected with cDNA expression plasmids encoding these two proteins and in transfected COS7 cells IL-4 augments association of FES with the IL-4R and tyrosine phosphorylation of both FES and the IL-4R. Through a deletion analysis of the IL-4R we have identified a putative FES-binding site in the cytoplasmic domain of the IL-4R.