Characterization of the membrane-bound and a soluble form of human IL-4 receptor α produced by alternative splicing

IL-4 plays a major role in IgE production. Its signal is conferred to effector cells through binding to the alpha chain of the membrane-bound human IL-4 receptor (huIL-4Ralpha). Here we present the genomic structure and organization of huIL-4Ralpha. The promotor region shows binding sites for several transcription factors involved in inflammatory processes. HuIL-4Ralpha has been shown to be organized differently to that of mouse IL-4Ralpha. A soluble form of huIL-4Ralpha is produced by alternative splicing of the huIL-4Ralpha gene (shuIL-4Ralpha/splice). Expression of the corresponding mRNA coding for the extracellular part of the receptor and an additional three amino acids is also shown. A second form of huIL-4Ralpha, i.e. shuIL-4Ralpha/prot, is produced by limited proteolysis of the receptor (shedding) and is already known. These results reveal a complex pattern for the regulation of the IL-4 pathway at the receptor level. The patterns of expression of all three receptor proteins as well as their individual meaning in the context of inflammation still have to be elucidated.