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Vav and Ras induce fibroblast transformation by overlapping signaling pathways which require c-Myc function
S Katzav1, G Packham, M Sutherland
1Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
Oncogene
|September 21, 1995
Summary
The Vav oncoprotein and Ras oncogenes activate distinct yet overlapping signaling pathways. Both pathways require c-Myc functions for fibroblast cell transformation, indicating a shared downstream effector.
Area of Science:
- Oncogene signaling pathways
- Cellular transformation mechanisms
- Signal transduction research
Background:
- The Vav oncoprotein acts as a GTP exchange factor for the Ras superfamily.
- Vav-induced fibroblast transformation differs morphologically from Ras-induced transformation.
- This suggests distinct signaling pathways mediating transformation.
Purpose of the Study:
- To investigate the relationship between Vav and Ras signaling pathways.
- To determine if Vav and Ras utilize common downstream effectors.
- To elucidate the role of c-Myc in Vav- and Ras-mediated transformation.
Main Methods:
- Utilized dominant-negative mutants of H-ras and proto-Vav (VavR695L).
- Assessed inhibition of Vav- and Ras-induced NIH3T3 fibroblast transformation.
- Investigated VavSH2 protein's effect on Xenopus oocyte maturation (GVBD).
- Examined the impact of dominant-negative c-Myc on transformation.
Main Results:
- Dominant-negative mutants partially inhibited both Vav- and Ras-induced transformation.
- VavSH2 protein induced GVBD and accelerated maturation, similar to Ras.
- Dominant-negative c-Myc abolished transformation induced by both Vav and Ras.
- Vav and Ras signaling pathways appear to overlap and converge on c-Myc.
Conclusions:
- Vav and Ras oncogenes activate distinct but overlapping signaling pathways.
- Fibroblast transformation by either Vav or Ras requires c-Myc function.
- These findings highlight a common downstream effector, c-Myc, in oncogenic transformation.