Alterations in Differentiation and Behavior of Monocytic Phagocytes in Transgenic Mice that Express Dominant Suppressors of ras Signaling
| Autor: | Michael C. Ostrowski, D Schenkman, D I Jin, M A Reddy, S B Jameson |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Macrophage colony-stimulating factor Transgene Cellular differentiation Cell Fluorescent Antibody Technique Gene Expression Mice Inbred Strains Mice Transgenic Biology Monocytes Mice Gene expression medicine Animals Humans RNA Messenger Promoter Regions Genetic Molecular Biology Transcription factor Macrophage Colony-Stimulating Factor Cell Differentiation Genes fms Cell Biology Cell cycle Urokinase-Type Plasminogen Activator Molecular biology Genes ras medicine.anatomical_structure Macrophages Peritoneal ras Proteins Female Guanosine Triphosphate Signal transduction Research Article Signal Transduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.15.2.693 |
| Popis: | To address the role of ras signaling in monocytic phagocytes in vivo, the expression of two dominant suppressors of in vitro ras signaling pathways, the carboxyl-terminal region of the GTPase-activating protein (GAP-C) and the DNA binding domain of the transcription factor ets-2, were targeted to this cell compartment. A 5-kb portion of the human c-fms proximal promoter was shown to direct expression of the transgenes to the monocytic lineage. As a result of the GAP-C transgene expression, ras-GTP levels were reduced in mature peritoneal macrophages by 70%. The terminal differentiation of monocytes was altered, as evidence by the accumulation of atypical monocytic cells in the blood. Mature peritoneal macrophages exhibited changes in colony-stimulating factor 1-dependent survival and structure. Further, expression of the colony-stimulating factor 1-stimulated gene urokinase plasminogen activator was inhibited in peritoneal macrophages. The results indicate that ras action is critical in monocytic cells after these cells have lost the capacity to traverse the cell cycle. |
| Databáze: | OpenAIRE |
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