Activation of the Jak/Stat signal transduction pathway in GH-treated rat osteoblast-like cells in culture

In this study, activation of the Jak/Stat signaling pathway was followed up on growth hormone (GH) stimulation, using the rat osteosarcoma cell-line UM R-106.01 that expresses high affinity GH receptors. The results show a GH-i nduced and sustained phosphorylation of Jak2 and Stat5 on tyrosine residues . The tyrosine phosphorylation status of Jak2 was increased in a dose-depen dent manner. In contrast to Jak2, tyrosine phosphorylation of Stat5 also el icited at 42 ng/ml GH, remained unchanged when GH concentration was raised up to 4200 ng/ml. DNA binding activity of StatS was also observed in respon se to GH. However, GH was unable to cause transactivation of reporter gene constructs harboring StatS binding sites (the GHREII from the rat spi 2.1 g ene promoter, and the LHRE from the rat beta -casein gene promoter), except in cells transiently transfected with either StatS cDNAs or the rat GHR cD NA. Altogether the results suggest that UMR-106.01 cells exhibit original f eatures of the GH-dependent Jak/Stat signaling pathway. (C) 2000 Elsevier S cience Ireland Ltd. All rights reserved.