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Rnd proteins function as RhoA antagonists by activating p190 RhoGAP
Krister Wennerberg1, Marie-Annick Forget, Shawn M Ellerbroek
1Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Current Biology : CB
|July 5, 2003
Summary
Rnd proteins counteract RhoA GTPase functions by interacting with p190 RhoGAP. This interaction enhances p190
Area of Science:
- Cellular Biology
- Molecular Signaling
- GTPase Regulation
Background:
- Rnd proteins (Rnd1, Rnd2, Rnd3/RhoE) are constitutively active Rho-family GTPases.
- Rnd proteins antagonize RhoA GTPase functions, but the mechanism is unclear.
- Potential mechanisms include effector sequestration, GEF inhibition, or GAP activation.
Purpose of the Study:
- To identify molecular effectors of Rnd proteins.
- To elucidate the mechanism by which Rnd proteins antagonize RhoA.
Main Methods:
- Identification of Rnd protein interactors.
- Use of Rnd3-RhoA chimeras and mutants.
- Experiments with p190-deficient cells.
Main Results:
- p190 RhoGAP (p190) identified as a Rnd protein interactor via a non-GAP domain region.
- Cellular effects of Rnd proteins are mediated by p190.
- Rnd proteins enhance p190's GTPase-activating protein (GAP) activity towards RhoA.
- Rnd3 expression reduces cellular RhoA-GTP levels in a p190-dependent manner.
Conclusions:
- p190 RhoGAPs are identified as effectors of Rnd proteins.
- A novel mechanism for Rnd protein antagonism of RhoA is demonstrated.