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Published on: January 27, 2014
RGS2/G0S8 is a selective inhibitor of Gqalpha function
S P Heximer1, N Watson, M E Linder
1Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Summary
Regulators of G protein signaling (RGS) proteins modulate cell signaling. This study identifies RGS2 as a highly selective inhibitor of Gqalpha, a novel finding for RGS protein function.
Area of Science:
- Molecular Biology
- Cell Signaling
- Biochemistry
Background:
- Regulators of G protein signaling (RGS) proteins are GTPase activating proteins that inhibit heterotrimeric G protein signaling.
- While most RGS proteins studied affect Gialpha family members, RGS2's specific G protein targets remained unidentified.
Purpose of the Study:
- To identify the specific G alpha (Galpha) proteins regulated by RGS2.
- To characterize the selectivity and potency of RGS2 as an inhibitor of G protein signaling.
Main Methods:
- Binding assays using brain membranes and purified recombinant G proteins (Gqalpha, Goalpha, Gialpha, Gsalpha, G12/13).
- GTPase activity assays to measure RGS protein function.
- Inhibition assays of phospholipase C (PLC) activation directed by Gqalpha in cell membranes and reconstituted phospholipid vesicles.
Main Results:
- RGS2 selectively binds Gqalpha but not other Galpha proteins (Gi, Go, Gs, G12/13) in brain membranes.
- RGS2 does not stimulate GTPase activity of Gsalpha or Gialpha family members, unlike RGS4.
- Both RGS2 and RGS4 inhibit Gq-directed phospholipase C activation, with RGS2 being 10-fold more potent in reconstituted systems.
Conclusions:
- RGS2 is a selective and potent inhibitor of Gqalpha function, identifying its first clear physiological role.
- This study presents the first example of an RGS protein specifically targeting Gqalpha.
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