Interleukin-13 receptor α′ but not a chain:: A functional component of interleukin-4 receptors

In hematopoietic cells, interleukin-2 receptor (IL-2R) gamma chain (termed gamma(c)) is shown to be a component of the IL-4R system, whereas in nonhematopoietic cells, gamma(c) is absent and it is not a component of the IL-4R system. Here, we show that the IL-13R alpha' chain (termed IL-13R alpha') but not the IL-13R alpha chain (termed IL-13R alpha) can substitute for gamma(c) and, thus, IL-13R alpha' forms a novel component of the IL-4R system, This conclusion was drawn on the basis of chemical cross-linking, immunoprecipitation, the ability of IL-10R alpha' but not IL-13R alpha to augment IL-4 binding affinity, and the requirement of IL-13R alpha' for IL-4-induced STAT6 activation in Chinese hamster ovary (CHO) cells transfected with various receptor subunits. Cotransfection of IL-4 receptor p140 (termed IL-4R beta) with gamma(c) or IL-13R alpha' increased IL-4 binding affinity and allowed for STAT6 activation in response to IL-4, However, cotransfection of all three chains did not further increase IL-4 binding or alter the extent of STAT6 activation suggesting that all three chains together do not seem to participate in IL-4 function. Instead, IL-4R beta heterodimerizes with gamma(c) or IL-13R alpha' and mediates STAT6 activation. Cotransfection of IL-4R beta with IL-13R alpha neither increased IL-4 binding affinity nor allowed for STAT6 activation in response to IL-4 indicating that IL-13R alpha does not convert binding affinity nor transmit signals for IL-4, Because IL-4 phosphorylates JAK1 and JAK2 tyrosine kinases in nonhematopoietic cells, we investigated whether JAK1 and JAK2 are required for IL-4-induced STAT6 activation in various transfectants. Cotransfection experiments with different chains of IL-4R and kinase-deficient JAK1 and JAK2 mutants in CHO cells showed that JAK1 and JAK2 are required for optimal activation of STAT6 in the alpha'beta transfectant but only partially in the beta gamma(c) transfectant, Taken together, our results show that IL-13R alpha' is a novel functional component of the IL-4R system and that JAK1 and JAK2 mediate IL-4-induced optimal activation of STAT6 in nonhematopoietic cells.