Transglutaminase 2 as a novel activator of LRP6/ß-catenin signaling.
Cell Signal
; 25(12): 2646-51, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-23993960
ABSTRACT
The ß-catenin signaling axis is critical for normal embryonic development and tissue homeostasis in adults. We have previously shown that extracellular enzyme transglutaminase 2 (TG2) activates ß-catenin signaling in vascular smooth muscle cells (VSMCs). In this study, we provide several lines of evidence that TG2 functions as an activating ligand of the LRP5/6 receptors. Specifically, we show that TG2 synergizes with LRP6 in the activation of ß-catenin-dependent gene expression in Cos-7 cells. Interfering with the LRP5/6 receptors attenuates TG2-induced activation of ß-catenin in Cos-7 cells. Further, we show that TG2 binds directly to the extracellular domain of LRP6, which is also able to act as a substrate for TG2-mediated protein cross-linking. Furthermore, inhibitors of TG2 protein cross-linking quench the observed TG2-induced ß-catenin activation, implicating protein cross-linking as a novel regulatory mechanism for this pathway. Together, our findings identify and characterize a new activating ligand of the LRP5/6 receptors and uncover a novel activity of TG2 as an agonist of ß-catenin signaling, contributing to the understanding of diverse developmental events and pathological conditions in which transglutaminase and ß-catenin signaling are implicated.
Palavras-chave
APC; Adenomatosis Polyposis Coli; E. coli; ECM; Escherichia coli; Extracellular matrix; Frizzled; Fzd; GSK3; Glycogen Synthase Kinase 3; Guinea pig liver TG2; Human TG2; LRP5 or LRP6; LRP5/6; MEFs; Mouse embryonic fibroblasts; TG2; TGases; Tissue transglutaminase; Transglutaminases; Transglutaminsase 2; VSMCs; Vascular smooth muscle cells; gpTG2; hTG2; ß-catenin
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Transglutaminases
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Proteínas de Ligação ao GTP
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Beta Catenina
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Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article