RECEPTORS FOR INTERLEUKIN-3 (IL-3) AND GROWTH-HORMONE MEDIATE AN IL-6-TYPE TRANSCRIPTIONAL INDUCTION IN THE PRESENCE OF JAK2 OR STAT3

To determine the specificity of signal transducer and activator of tra nscription (STAT) protein activation by box 3 motif-deficient hematopo ietin receptors, expression vectors encoding the receptors for growth hormone, interleukin-3 (IL-3), and IL-4 were transiently transfected i nto COS-1 cells, together with expression vectors for Janus kinases (J AKs) and STAT proteins. Each receptor mediated a dose-dependent activa tion of STAT1 and STAT3, and for IL-3R and GHR this process was enhanc ed by JAK2, The data suggest that a box 3 motif in the cytoplasmic dom ain of the signal-transducing receptor subunit was not absolutely requ ired for linking the receptor to the JAK/STAT pathway. Transfection of the receptors, in combination with STAT3, into HepG2 cells reconstitu ted a cytokine-dependent stimulation of gene transcription through IL- 6 response elements, providing evidence for a functional role of STAT3 in controlling gene expression.