Oncogenic v-Abl tyrosine kinase can inhibit or stimulate growth, depending on the cell context.
The v-abl oncogene of Abelson murine leukemia virus (A-MuLV) induces two opposite phenotypes in NIH3T3 cells. In the majority of cells, v-abl causes a growth arrest at the G1 phase of the cell cycle; while in a minority of cells, v-abl abrogates the requirement for growth factors. Using temperature sensitive mutants, it can be demonstrated that v-Abl tyrosine kinase is required for growth inhibition or stimulation. The two phenotypes are not caused by mutations or differences in the expression of v-Abl, but are dependent on the cell context. Two stable subclones of NIH3T3 cells have been isolated that exhibit similar morphology and growth characteristics. However, upon infection with A-MuLV, the 'positive' cells become serum- and anchorage-independent, whereas the 'negative' cells become arrested in G1. The positive phenotype is dominant, shown by cell fusion, and treatment with 5-azacytidine converts the negative cells to the positive phenotype. Activation of v-Abl tyrosine kinase induces the serum-responsive genes in the positive but not in the negative cells. Transactivation of the c-fos promoter by v-Abl in transient assays is also restricted to the positive cells. These results show that v-Abl tyrosine kinase is not an obligatory activator of growth, but requires a permissive cellular context to manifest its mitogenic function.
Renshaw
M W
MW
Department of Biology, University of California, San Diego, La Jolla 92093-0116.
Kipreos
E T
ET
Albrecht
M R
MR
Wang
J Y
JY
D016475:3T3 Cells; D000011:Abelson murine leukemia virus / Q000235:genetics; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D002459:Cell Fusion; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells; D016313:Genes, abl; D014644:Genetic Variation; D007700:Kinetics; D051379:Mice; D016374:Oncogene Proteins v-abl / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D016374:Oncogene Proteins v-abl; D011505:Protein-Tyrosine Kinases