Structure of and signal transduction through interleukin-4 and interleukin-13 receptors (Review)

We have recently demonstrated that two different forms of IL-4R exist; classical or alternative. The classical IL-4R is predominantly expressed in hematopoietic cells and consist of IL-4R beta and IL-2R gamma(c) (gamma(c)) chains. On the other hand, alternative form of IL-4R is predominantly expressed in nonhematopoietic cells and consists of IL-4R beta and IL-13R alpha' chains. Moreover, the alternative form of lL-4R is also utilized as a functional component IL-13R complex. It has been shown that the phosphorylation and activation of JAK3 tyrosine kinase is crucial for IL-4 activation of STAT6 in hematopoietic cells. However, we have recently demonstrated that nonhematopoietic cells lack JAK3 expression. We also demonstrated that in these cells, STAT6 activation is mediated through JAK1 and JAK2 tyrosine kinases instead. Furthermore, our results show that IL-4 and IL-13 signals are transmitted through the alternative form of IL-4R in these cells. Thus, major differences exist between hematopoietic and non-hematopoietic cells with regard to structure and signal transduction through IL-4R and IL-13R systems.