期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 39, 期 5, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.00422-18
关键词
beta-catenin; G-alpha subunits; G-proteins; Pasteurella multocida toxin
资金
- King's College London Dental Institute Studentship Fund
- King's College London Graduate Scholarship Scheme
- BBSRC [BB/1021922/1]
- BBSRC [BB/I021922/1, BB/E013872/1] Funding Source: UKRI
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 beta-catenin signaling. However, the link between G-proteins and beta-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 beta-catenin using G-alpha subunit genetic knockout and knockdown approaches. The Pasteurella multocida toxin was utilized as a unique tool to activate G-proteins, with LiCl treatment serving as a beta-catenin signaling agonist. The results show that Pasteurella multocida toxin (PMT) significantly enhanced LiCl-induced active beta-catenin levels in HEK293T cells and mouse embryo fibroblasts. Evaluation of the effect of specific G-alpha proteins on the regulation of beta-catenin showed that G(q/11) and G(12/13) knockout cells had significantly higher levels of active and total beta-catenin than wild-type cells. The stimulation of active beta-catenin by PMT and LiCl was lost upon both constitutive and transient knockdown of G(12) and G(13) but not G(q). Based on our results, we conclude that endogenous G-alpha proteins are negative regulators of active beta-catenin; however, PMT-activated G-alpha subunits positively regulate LiCl-induced beta-catenin expression in a G(12/13)-dependent manner. Hence, G-alpha subunit regulation of beta-catenin is context dependent.
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