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Oncogenic v‐Abl tyrosine kinase can inhibit or stimulate growth, depending on the cell context.
Author(s) -
Renshaw M.W.,
Kipreos E.T.,
Albrecht M.R.,
Wang J.Y.
Publication year - 1992
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1992.tb05488.x
Subject(s) - biology , context (archaeology) , tyrosine kinase , microbiology and biotechnology , abl , kinase , proto oncogene tyrosine protein kinase src , cell growth , cancer research , signal transduction , genetics , paleontology
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.