Receptors for Interleukin-3 (IL-3) and Growth Hormone Mediate an IL-6-Type Transcriptional Induction in the Presence of JAK2 or STAT3

Abstract

To determine the specificity of signal transducer and activator of transcription (STAT) protein activation by box 3 motif-deficient hematopoietin receptors, expression vectors encoding the receptors for growth hormone, interleukin-3 (IL-3), and IL-4 were transiently transfected into COS-1 cells, together with expression vectors for Janus kinases (JAKs) and STAT proteins. Each receptor mediated a dose-dependent activation of STAT1 and STAT3, and for IL-3R and GHR this process was enhanced by JAK2. The data suggest that a box 3 motif in the cytoplasmic domain of the signal-transducing receptor subunit was not absolutely required for linking the receptor to the JAK/STAT pathway. Transfection of the receptors, in combination with STATS, into HepG2 cells reconstituted a cytokine-dependent stimulation of gene transcription through IL-6 response elements, providing evidence for a functional role of STAT3 in controlling gene expression. © 1995 by The American Society of Hematology.