The regulator of G protein signaling domain of axin selectively interacts with Galpha12 but not Galpha13.
Axin, a negative regulator of the Wnt signaling pathway, contains a canonical regulator of G protein signaling (RGS) core domain. Herein, we demonstrate both in vitro and in cells that this domain interacts with the alpha subunit of the heterotrimeric G protein G12 but not with the closely related Galpha13 or with several other heterotrimeric G proteins. Axin preferentially binds the activated form of Galpha12, a behavior consistent with other RGS proteins. However, unlike other RGS proteins, that of axin (axinRGS) does not affect intrinsic GTP hydrolysis by Galpha12. Despite its inability to act as a GTPase-activating protein, we demonstrate that in cells, axinRGS can compete for Galpha12 binding with the RGS domain of p115RhoGEF, a known G12-interacting protein that links G12 signaling to activation of the small G protein Rho. Moreover, ectopic expression of axinRGS specifically inhibits Galpha12-directed activation of the Rho pathway in MDA-MB 231 breast cancer cells. These findings establish that the RGS domain of axin is able to directly interact with the alpha subunit of heterotrimeric G protein G12 and provide a unique tool to interdict Galpha12-mediated signaling processes.
Duke Scholars
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transfection
- Signal Transduction
- Repressor Proteins
- Protein Structure, Tertiary
- Pharmacology & Pharmacy
- Humans
- GTP-Binding Proteins
- GTP-Binding Protein alpha Subunits, G12-G13
- Cell Line
- Axin Protein
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transfection
- Signal Transduction
- Repressor Proteins
- Protein Structure, Tertiary
- Pharmacology & Pharmacy
- Humans
- GTP-Binding Proteins
- GTP-Binding Protein alpha Subunits, G12-G13
- Cell Line
- Axin Protein