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Temperature-sensitive transformation by an Abelson virus mutant encoding an altered SH2 domain.
C A Mainville1, K Parmar, I Unnikrishnan
1Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Journal of Virology
|February 13, 2001
Summary
A novel Abelson murine leukemia virus (Ab-MLV) mutant exhibits temperature-dependent transformation of cells. This suggests alterations in the v-Abl protein
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Abelson murine leukemia virus (Ab-MLV) encodes v-Abl tyrosine kinase, crucial for cell transformation.
- v-Abl kinase activity is essential for transformation, but other domains, like SH2, modulate this.
- The SH2 domain's FLVRES motif forms a phosphotyrosine-binding pocket for substrate interaction.
Purpose of the Study:
- To investigate the impact of SH2 domain alterations on Ab-MLV-mediated transformation.
- To characterize the Ab-MLV mutant P120/R273K, which has an altered v-Abl phosphotyrosine-binding pocket.
Main Methods:
- Infection of NIH 3T3 and pre-B cells with wild-type and P120/R273K Ab-MLV mutants.
- Assessment of cell transformation efficiency at different temperatures (34°C and 39.5°C).
- Analysis of Shc phosphorylation and c-Myc expression levels.
Main Results:
- The P120/R273K mutant displayed a temperature-dependent transformation phenotype.
- Transformation efficiency was significantly reduced at 39.5°C compared to 34°C.
- Reduced Shc phosphorylation and c-Myc induction correlated with decreased transformation at higher temperatures.
Conclusions:
- Alterations in the v-Abl FLVRES pocket affect substrate interaction in a temperature-dependent manner.
- The P120/R273K mutant represents a novel type of temperature-sensitive Abelson virus.
- This study highlights the complex role of the SH2 domain in v-Abl's oncogenic function.