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An essential role for Rac in Ras transformation.
- Source :
-
Nature [Nature] 1995 Mar 30; Vol. 374 (6521), pp. 457-9. - Publication Year :
- 1995
-
Abstract
- The GTPase Rac1 is a key component in the reorganization of the actin cytoskeleton that is induced by growth factors or oncogenic Ras1. Here we investigate the role of Rac1 in cell transformation and show that Rat1 fibroblasts expressing activated Val-12 Rac1 (Rac1 with valine at residue 12) display all the hallmarks of malignant transformation. In a focus-forming assay in NIH3T3 fibroblasts to measure the efficiency of transformation, we found that dominant-negative Asn-17 Rac1 inhibited focus formation by oncogenic Ras, but not by RafCAAX, a Raf kinase targeted to the plasma membrane by virtue of the addition of a carboxyterminal localization signal from K-Ras. This indicates that Rac is essential for transformation by Ras. In addition, Val-12 Rac1 synergizes strongly with RafCAAX in focus-formation assays, indicating that oncogenic Ras drives both the Rac and MAP-kinase pathways, which cooperate to cause transformation.
- Subjects :
- 3T3 Cells
Amino Acid Sequence
Animals
Asparagine physiology
GTP-Binding Proteins genetics
Mice
Molecular Sequence Data
Protein Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-raf
Rats
Transfection
Valine physiology
rac GTP-Binding Proteins
Cell Transformation, Neoplastic genetics
GTP-Binding Proteins physiology
Genes, ras
Subjects
Details
- Language :
- English
- ISSN :
- 0028-0836
- Volume :
- 374
- Issue :
- 6521
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 7700355
- Full Text :
- https://doi.org/10.1038/374457a0