Related Experiment Videos
G2A is an oncogenic G protein-coupled receptor.
1Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill 27599-7038, USA.
Oncogene
|August 22, 2000
Summary
The G2A protein, previously thought to be a tumor suppressor, is actually oncogenic. It promotes cell transformation and tumorigenicity by activating Rho GTPases, challenging prior research findings.
Area of Science:
- Cell Biology
- Oncology
- Molecular Biology
Background:
- G2A, a cell surface protein, was recently proposed as a tumor suppressor.
- Its proposed role was based on counteracting oncogenic tyrosine kinase Bcr-Abl in pre-B cells and fibroblasts.
Purpose of the Study:
- To investigate the role of G2A in cell transformation.
- To determine the mechanism by which G2A influences cellular phenotypes.
Main Methods:
- Screening cDNA libraries for clones inducing oncogenic transformation.
- Retroviral transduction and transfection of NIH3T3 cells to express G2A.
- Assessing transformation phenotypes, including loss of contact inhibition and tumorigenicity.
- Investigating downstream signaling pathways involving G proteins and Rho GTPases.
Main Results:
- G2A expression induced phenotypes characteristic of oncogenic transformation in NIH3T3 cells.
- G2A enhanced the transforming ability of a weakly oncogenic Raf-1.
- G2A expression altered cell morphology and cytoskeleton, mimicking Galpha13.
- G2A-induced transformation was dependent on RhoA activation and suppressed by LscRGS, indicating a link to Galpha13 signaling.
Conclusions:
- G2A is a potent oncogene, capable of transforming cells independently or cooperatively.
- G2A likely signals through Galpha13 to activate Rho GTPases, mediating its oncogenic effects.
- These findings contradict the previous hypothesis of G2A as a tumor suppressor.