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

Interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor, and IL-5 receptors (IL-3R, GMR, and IL-5R) are composed of the alpha c hain specific to each and the common beta chain, and both the alpha an d beta subunits are members of the cytokine receptor superfamily. We p reviously showed that the high-affinity human GMR reconstituted by cot ransfecting the alpha and beta 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 fibrobla st NIH3T3 cells. These results indicated that molecules, such as tyros ine kinase, unique to hematopoietic cells are not essential to transdu ce signals. In this study, the function of the alpha subunit of GMR wa s compared with those of IL-3R and IL-5R by cotransfecting human cDNAs encoding the alpha subunit of IL-3R or IL-5R and the common beta subu nit into BA/F3 or NIH3T3 cells. We found that the reconstituted human IL-3R, in response to hIL-3, transduced signals to activate transcript ion 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 indicate d that the alpha subunits of IL-3R and IL-5R have properties similar t o those of the GMR alpha subunit. In contrast, transfected human IL-4 receptor (hIL-4R) cDNA, which weakly activated c-fos promoter and indu ced 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 lac k some component or components required fdr signal transduction by hIL -4R.