G-Alpha Subunit Abundance and Activity Differentially Regulate β-Catenin Signaling

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2018 Dec 19

PMID 30559307

Citations 2

Authors

Arshiya Banu

Karen J Liu

Alistair J Lax

Agamemnon E Grigoriadis

Affiliations

Soon will be listed here.

Abstract

Heterotrimeric G proteins are signal transduction proteins involved in regulating numerous signaling events. In particular, previous studies have demonstrated a role for G-proteins in regulating β-catenin signaling. However, the link between G-proteins and β-catenin signaling is controversial and appears to depend on G-protein specificity. We describe a detailed analysis of a link between specific G-alpha subunits and β-catenin using G-alpha subunit genetic knockout and knockdown approaches. The toxin was utilized as a unique tool to activate G-proteins, with LiCl treatment serving as a β-catenin signaling agonist. The results show that toxin (PMT) significantly enhanced LiCl-induced active β-catenin levels in HEK293T cells and mouse embryo fibroblasts. Evaluation of the effect of specific G-alpha proteins on the regulation of β-catenin showed that G and G knockout cells had significantly higher levels of active and total β-catenin than wild-type cells. The stimulation of active β-catenin by PMT and LiCl was lost upon both constitutive and transient knockdown of G and G but not G Based on our results, we conclude that endogenous G-alpha proteins are negative regulators of active β-catenin; however, PMT-activated G-alpha subunits positively regulate LiCl-induced β-catenin expression in a G-dependent manner. Hence, G-alpha subunit regulation of β-catenin is context dependent.

Citing Articles

Pasteurella multocida toxin - lessons learned from a mitogenic toxin.

Kubatzky K Front Immunol. 2023; 13:1058905.

PMID: 36591313 PMC: 9800868. DOI: 10.3389/fimmu.2022.1058905.

In Vivo Targets of Toxin.

Banu A, Lax A, Grigoriadis A Int J Mol Sci. 2020; 21(8).

PMID: 32326543 PMC: 7215291. DOI: 10.3390/ijms21082739.

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