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The regulator of G protein signaling domain of axin selectively interacts with Galpha12 but not Galpha13.

Publication ,  Journal Article
Stemmle, LN; Fields, TA; Casey, PJ
Published in: Mol Pharmacol
October 2006

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

Mol Pharmacol

DOI

ISSN

0026-895X

Publication Date

October 2006

Volume

70

Issue

4

Start / End Page

1461 / 1468

Location

United States

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

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Stemmle, L. N., Fields, T. A., & Casey, P. J. (2006). The regulator of G protein signaling domain of axin selectively interacts with Galpha12 but not Galpha13. Mol Pharmacol, 70(4), 1461–1468. https://doi.org/10.1124/mol.106.023705
Stemmle, Laura N., Timothy A. Fields, and Patrick J. Casey. “The regulator of G protein signaling domain of axin selectively interacts with Galpha12 but not Galpha13.Mol Pharmacol 70, no. 4 (October 2006): 1461–68. https://doi.org/10.1124/mol.106.023705.
Stemmle LN, Fields TA, Casey PJ. The regulator of G protein signaling domain of axin selectively interacts with Galpha12 but not Galpha13. Mol Pharmacol. 2006 Oct;70(4):1461–8.
Stemmle, Laura N., et al. “The regulator of G protein signaling domain of axin selectively interacts with Galpha12 but not Galpha13.Mol Pharmacol, vol. 70, no. 4, Oct. 2006, pp. 1461–68. Pubmed, doi:10.1124/mol.106.023705.
Stemmle LN, Fields TA, Casey PJ. The regulator of G protein signaling domain of axin selectively interacts with Galpha12 but not Galpha13. Mol Pharmacol. 2006 Oct;70(4):1461–1468.

Published In

Mol Pharmacol

DOI

ISSN

0026-895X

Publication Date

October 2006

Volume

70

Issue

4

Start / End Page

1461 / 1468

Location

United States

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