Received for publication February 22, 2006.
Revised July 19, 2006.
Accepted for publication July 25, 2006.

The RGS domain of Axin selectively interacts with Galpha12 but not Galpha13

Abstract

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 G13 or with several other heterotrimeric G proteins. Axin preferentially binds the activated form of G12, a behavior consistent with other RGS proteins. However, unlike other RGS proteins, the RGS domain of axin (axinRGS) does not affect intrinsic GTP hydrolysis by G12. Despite its inability to act as a GTPase activating protein, we demonstrate that in cells axinRGS can compete for G12 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 G12 -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 G12-mediated signaling processes.

Key words: G12,13;other G's, G protein regulation, RGS proteins

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