Activation of the JAK-STAT signal transduction pathway by oncostatin-M cultured human and mouse osteoblastic cells.
Oncastatin M (OSM) is one member of the leukemia inhibitory factor/interleukin-6 family of cytokines that has been shown to be a growth regulatory molecule. In osteoblastic cultures, OSM causes marked phenotypic changes and the enhanced secretion of interleukin-6. In this study, we have shown that stimulation of murine and human osteoblastic cultures and a human osteosarcoma cell line with OSM resulted in the tyrosine phosphorylation of a number of cellular proteins including members of both the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) family of signaling proteins. The JAKs, a family of intracellular kinases, and the STATs, a family of transcription factors, have both previously been shown to be tyrosine phosphorylated and activated in response to various cytokines, interferons, and growth factors in cells of non-skeletal origin. Using three different sources of cells of the osteoblast lineage, we demonstrate that OSM induces a rapid but transient tyrosine phosphorylation of the three JAK family members tested, JAK1, JAK2 and Tyk2. In addition, two members of the STAT family, Stat1alpha and Stat3, are tyrosine phosphorylated in osteoblastic cells in culture in response to OSM. OSM activation of this pathway in cells of the osteoblast lineage will result in the transcription of specific genes that ultimately may be associated with osteoblast function.
Levy
J B
JB
Department of Orthopaedics, Yale University School of Medicine, New Haven, Connecticut 06520-8071, USA.
Schindler
C
C
Raz
R
R
Levy
D E
DE
Baron
R
R
Horowitz
M C
MC
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D051379:Mice; D008810:Mice, Inbred C57BL; D053683:Oncostatin M; D010006:Osteoblasts / Q000502:physiology*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D016207:Cytokines; D004268:DNA-Binding Proteins; D050832:Interferon-Stimulated Gene Factor 3; C508351:OSM protein, human; C508352:Osm protein, mouse; D010455:Peptides; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C079868:gamma interferon activation factor; D053683:Oncostatin M; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; C507905:Jak1 protein, mouse; C507926:Jak2 protein, mouse; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053634:TYK2 Kinase; C070139:TYK2 protein, human; C499356:Tyk2 protein, mouse