THE MEMBRANE PROXIMAL REGION OF THE CYTOPLASMIC DOMAIN OF THE GROWTH-HORMONE RECEPTOR IS INVOLVED IN THE ACTIVATION OF STAT-3

Growth hormone receptor (GHR) signaling involves activation of the Jan us Kinases (Jak) and of Stat proteins (signal transducers and activato rs of transcription). Growth hormone (GH) induces transcriptional acti vation of c-fos gene and the c-sis inducible element (SLE) of its prom oter was shown to bind the Stat proteins. Using cells co-transfected,v ith GHR and Stat 3 expression vectors, we directly demonstrate that GH induces tyrosine phosphorylation of Stat 3 and its binding to the SIE probe. We showed, using mutant forms of GHR, that only the cytoplasmi c membrane proximal domain of the receptor, including a conserved prol ine rich region (box 1), is required for this effect.