Activation of early response genes and cell proliferation by human interleukin-3, granulocyte-macrophage colony-stimulating factor, and interleukin-5 receptors: Comparison with human interleukin-4 receptor signaling

Abstract

Interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor, and IL-5 receptors (IL-3R, GMR, and IL-5R) are composed of the α chain specific to each and the common β chain, and both the α and β subunits are members of the cytokine receptor superfamily. We previously showed that the high-affinity human GMR reconstituted by cotransfecting the α and β chain cDNA clones transduces signals in response to hGM-CSF to activate transcription of c-fos, c-jun, and c-myc proto-oncogenes in mouse proB cell line BA/F3 or in mouse fibroblast NIH3T3 cells. These results indicated that molecules, such as tyrosine kinase, unique to hematopoietic cells are not essential to transduce signals. In this study, the function of the α subunit of GMR was compared with those of IL-3R and IL-5R by cotransfecting human cDNAs encoding the α subunit of IL-3R or IL-5R and the common β subunit into BA/F3 or NIH3T3 cells. We found that the reconstituted human IL-3R, in response to hIL-3, transduced signals to activate transcription of c-fos promoter and induced DNA synthesis in both types of cells in a manner similar to hGMR. Likewise, hIL-5 activates c-fos promoter in transfected NIH3T3 cells expressing hIL-5R. These results indicated that the α subunits of IL-3R and IL-5R have properties similar to those of the GMR α subunit. In contrast, transfected human IL-4 receptor (hIL-4R) cDNA, which weakly activated c-fos promoter and induced DNA synthesis in BA/F3 cells, failed to elicit these activities in NIH3T3 cells in response to hIL-4. It is likely that NIH3T3 cells lack some component or components required for signal transduction by hIL-4R. (J ALLERGY CLIN IMMUNOL 1994;94:605-11.)