Regulation of GSK-3β and β-Catenin by Gαq in HEK293T cells

Sara Salmanian, S. Mahmoud A Najafi*, Maryam Rafipour, Maryam Rezaei Arjomand, Hamideh Shahheydari, Sara Ansari, Leily Kashkooli, S. Javad Rasouli, Marie Saghaeian Jazi, Tayebeh Minaei

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Recent studies have shown that heterotrimeric G proteins are involved in the regulation of the canonical Wnt/β-Catenin pathway. However, the mechanism(s) behind this involvement is (are) poorly understood. Our previous results have shown that activation of Gαq in Xenopus oocytes leads to inhibition of GSK-3β and stabilization of the β-Catenin protein, suggesting that Gαq might stabilize β-Catenin via inhibition of GSK-3β. In this study, we have observed similar results in HEK293T cells. In these cells optimal activation of endogenous Gαq by expressing M3-muscarinic acetylcholine receptor (with or without carbachol treatment), or exposing the cells to thrombin led to an increase of 2 to 3-fold in endogenous cytoplasmic β-Catenin protein levels. In addition, expression of the activated mutant of Gαq (GαqQL) dramatically enhanced accumulation of exogenous β-Catenin with no effect on β-catenin (CTNNB1) gene transcription. The Gαq-mediated cellular accumulation of β-Catenin was blocked by expression of a minigene encoding a Gαq specific inhibitory peptide but not by a minigene encoding a Gαs blocking peptide. Also, expression of GαqQL led to a significant reduction in GSK-3β kinase activity, supporting the idea that the positive role of Gαq signaling in inducing cellular accumulation of β-Catenin is mediated through inhibition of GSK-3β.

Original languageEnglish
Pages (from-to)577-582
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume395
Issue number4
DOIs
Publication statusPublished - 14 May 2010
Externally publishedYes

Keywords

  • β-Catenin
  • Gαq
  • GSK-3β
  • Wnt signaling

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