Transglutaminase 2 as a novel activator of LRP6/β-catenin signaling

S. Deasey, D. Nurminsky, S. Shanmugasundaram, F. Lima, M. Nurminskaya

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


The β-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 β-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 β-catenin-dependent gene expression in Cos-7 cells. Interfering with the LRP5/6 receptors attenuates TG2-induced activation of β-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 β-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 β-catenin signaling, contributing to the understanding of diverse developmental events and pathological conditions in which transglutaminase and β-catenin signaling are implicated.

Original languageEnglish
Pages (from-to)2646-2651
Number of pages6
JournalCellular Signalling
Issue number12
StatePublished - Dec 2013

Bibliographical note

Funding Information:
This study was supported by the National Institute of Health , grants HL093305 and DK071920 (to M.N.). We are very grateful to Dr. B. Williams for sharing the LRP5 null embryonic fibroblasts used in these studies, to Dr. X He for providing the LRP6-expression vector and to Dr. S Du for providing zebrafish and facilities to perform injections.


  • LRP5/6
  • Transglutaminsase 2
  • ß-catenin

ASJC Scopus subject areas

  • Cell Biology


Dive into the research topics of 'Transglutaminase 2 as a novel activator of LRP6/β-catenin signaling'. Together they form a unique fingerprint.

Cite this