ONCOSTATIN M ACTIVATES STAT DNA BINDING AND TRANSCRIPTIONAL ACTIVITY IN PRIMARY HUMAN FETAL ASTROCYTES: LOW- AND HIGH-PASSAGE CELLS HAVE DISTINCT PATTERNS OF STAT ACTIVATION
| Autor: | Timothy S. Schaefer, Shuguang Wang, Laura K. Schaefer |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Chloramphenicol O-Acetyltransferase
STAT3 Transcription Factor Transcriptional Activation Cytoplasm Time Factors Transcription Genetic Immunoblotting Immunology Cell Culture Techniques Oncostatin M Transfection Biochemistry Cell Line Genes Reporter Humans Immunology and Allergy alpha-Macroglobulins STAT1 STAT3 Molecular Biology STAT4 Cells Cultured Genes Dominant STAT6 Cell Nucleus biology JAK-STAT signaling pathway Oncostatin M receptor DNA Proto-Oncogene Proteins c-sis Hematology Embryo Mammalian beta-Galactosidase Molecular biology Growth Inhibitors DNA-Binding Proteins Enzyme Activation STAT1 Transcription Factor Astrocytes Trans-Activators biology.protein Peptides Plasmids Protein Binding |
| Zdroj: | Cytokine. 12:1647-1655 |
| ISSN: | 1043-4666 |
| DOI: | 10.1006/cyto.2000.0774 |
| Popis: | In this study we explored the activation of the JAK/Stat pathway by gp 130 family cytokines in primary human astrocytes. We report that of four gp 130 cytokines tested, only oncostatin M (OnM) resulted in the activation of Stat molecules. To test that the induced molecules were transcriptionally active, transcription from a Stat-responsive reporter plasmid (from the acute-phase gene α-2 macroglobulin) transiently transfected into astrocytes was assessed after activation by OnM and was blocked by cotransfection with dominant-negative Stat3 encoding plasmids strongly suggesting that the activation was Stat-mediated. While DNA binding complexes comprised of both Stat1 and Stat3 were induced in low-passage cells, only those containing Stat3 were formed by extracts from high-passage cells. Stat1 protein was detected in the cytoplasm of high-passage cells indicating that the inability to form SIF-B and -C complexes was due to a lack of activation of Stat1 rather than a lack of expression. These results indicate a fundamental difference between low- and high-passage astrocytes in response to cytokine treatment that might result in distinct patterns of gene expression through altered ratios of activated Stat3 and Stat1. |
| Databáze: | OpenAIRE |
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