1. ERK signalling and oncogene transformation are not impaired in cells lacking A-Raf
- Author
-
Richard Marais, Martin Hüser, Michelle Kiernan, Antonio Chiloeches, Kathryn Mercer, and Catrin Pritchard
- Subjects
Male ,MAPK/ERK pathway ,Cancer Research ,MAP Kinase Signaling System ,Cellular differentiation ,Blotting, Western ,Apoptosis ,Biology ,Polymerase Chain Reaction ,Proto-Oncogene Proteins A-raf ,Cell Line ,Mice ,Genetics ,Animals ,Cell Lineage ,Protein kinase A ,Molecular Biology ,Oncogene ,Kinase ,Stem Cells ,Teratoma ,Cell Differentiation ,Oncogenes ,Fibroblasts ,Cell biology ,Enzyme Activation ,Proto-Oncogene Proteins c-raf ,Genes, src ,Cell Transformation, Neoplastic ,Genes, ras ,Immunology ,Mitogen-Activated Protein Kinases ,Signal transduction ,Stem cell ,Cell Division ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Previous studies have indicated an important role for the Raf family of protein kinases in controlling cellular responses to extracellular stimuli and activated oncogenes, through their ability to activate the MEK/ERKs. To investigate the specific role of A-Raf in this process we generated A-Raf deficient mouse embryonic fibroblasts (MEFs) and embryonic stem (ES) cells by gene targeting and characterized their ability to undergo proliferation, differentiation, apoptosis, ERK activation, and transformation by oncogenic Ras and Src. The A-Raf deficient cells are not disrupted for any of these processes, despite the fact that this protein is normally expressed at high levels in both cell types. This implies either that A-Raf plays no role in MEK/ERK activation, that its function is fully compensated by other Raf proteins or MEK kinases or that its role in MEK/ERK activation is highly tissue-specific. Interestingly, B-Raf and Raf-1 activity towards MEK as measured by the immunoprecipitation kinase cascade assay are both significantly increased in the A-Raf deficient MEFs.
- Published
- 2002