RT Journal Article
SR Electronic
T1 The Regulator of G Protein Signaling Domain of Axin Selectively Interacts with Gα<sub>12</sub> but Not Gα<sub>13</sub>
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1461
OP 1468
DO 10.1124/mol.106.023705
VO 70
IS 4
A1 Stemmle, Laura N.
A1 Fields, Timothy A.
A1 Casey, Patrick J.
YR 2006
UL http://molpharm.aspetjournals.org/content/70/4/1461.abstract
AB 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 α subunit of the heterotrimeric G protein G12 but not with the closely related Gα13 or with several other heterotrimeric G proteins. Axin preferentially binds the activated form of Gα12, a behavior consistent with other RGS proteins. However, unlike other RGS proteins, that of axin (axinRGS) does not affect intrinsic GTP hydrolysis by Gα12. Despite its inability to act as a GTPase-activating protein, we demonstrate that in cells, axinRGS can compete for Gα12 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 Gα12-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 α subunit of heterotrimeric G protein G12 and provide a unique tool to interdict Gα12-mediated signaling processes. The American Society for Pharmacology and Experimental Therapeutics