Sharing of receptor subunits and signal transduction pathway between the IL-4 and IL-13 receptor system

In this review, we summarize the subunit structure of the interleukin (IL)- 4 and IL-13 receptor system and the molecular mechanism of signals through the cytokine receptor systems. We have demonstrated that two different form s of IL-4R exist, classical and alternative. Classical IL-4R is predominant ly expressed in hematopoietic cells and consists of IL-4R p140 (beta) and I L-2R gamma(gamma(c)) chains. The alternative form of IL-4R is predominantly expressed in nonhematopoietic cells and consists of IL-4R beta and n-13R a lpha' chains. Moreover, the alternative form of IL-4R is also used as a fun ctional component in the IL-13R complex. For signal transduction through IL -4R and IL-13R, we have demonstrated that in nonhematopoietic cells, Janus protein tyrosine kinase (JAK) 2 is phosphorylated and activated instead of JAK3 tyrosine kinase. While JAK3 is required for signal transducer and acti vator of transcription-6 (STAT6) activation in hematopoietic cells, we rece ntly demonstrated that in nonhematopoietic cells JAK2 is required for STAT6 activation for the alternative form of IL-4R. Thus, a major difference exi sts between hematopoietic and nonhematopoietic cells with regard to structu re and signal transduction through the IL-4R and IL-13R systems. (C) 1999 T he Japanese Society of Hematology.