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 upon growth hormone (GH) stimulation, using the rat osteosarcoma cell-line UMR-106.01 that expresses high affinity GH receptors. The results show a GH-induced and sustained phosphorylation of Jak2 and Stat5 on tyrosine residues. The tyrosine phosphorylation status of Jak2 was increased in a dose-dependent manner. In contrast to Jak2, tyrosine phosphorylation of Stat5, also elicited at 42 ng/ml GH, remained unchanged when GH concentration was raised up to 4200 ng/ml. DNA binding activity of Stat5 was also observed in response to GH. However, GH was unable to cause transactivation of reporter gene constructs harboring Stat5 binding sites (the GHREII from the rat spi 2.1 gene promoter, and the LHRE from the rat beta-casein gene promoter), except in cells transiently transfected with either Stat5 cDNAs or the rat GHR cDNA. Altogether the results suggest that UMR-106.01 cells exhibit original features of the GH-dependent Jak/Stat signaling pathway.
Gerland
K
K
Laboratoire d'Histologie Embryologie (LHEA), UFR des Sciences Médicales, 1, rue Haute de Reculée, 49045 cedex, Angers, France.
Bataillé-Simoneau
N
N
Baslé
M
M
Fourcin
M
M
Gascan
H
H
Mercier
L
L
D000818:Animals; D016895:Culture Media, Serum-Free; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D019382:Human Growth Hormone / Q000494:pharmacology*; D053614:Janus Kinase 2; D008894:Milk Proteins; D012516:Osteosarcoma; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051381:Rats; D011986:Receptors, Somatotropin / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects* / Q000235:genetics; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D019382:Human Growth Hormone; D004247:DNA; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507927:Jak2 protein, rat; D053614:Janus Kinase 2