Work

A Novel Mechanism for Wnt Activation of Canonical Signaling through the LRP6 Receptor

Year: 2003

Type: article

Abstract: LDL receptor-related protein 6 (LRP6) is a Wnt coreceptor in the canonical signaling pathway, which plays essential roles in embryonic development. We demonstrate here that wild-type LRP6 forms an inactive dimer through interactions mediated by epidermal growth factor repeat regions within the extracellular domain. A truncated LRP6 comprising its transmembrane and cytoplasmic domains is expressed as a constitutively active monomer whose signaling ability is inhibited by forced dimerization. Conversely, Wnts are shown to activate canonical signaling through LRP6 by inducing an intracellular conformational switch which relieves allosteric inhibition imposed on the intracellular domains. Thus, Wnt canonical signaling through LRP6 establishes a novel mechanism for receptor activation which is opposite to the general paradigm of ligand-induced receptor oligomerization.

Source: Molecular and Cellular Biology

DOI: 10.1128/mcb.23.16.5825-5835.2003

Authors: Guizhong Liu, Anna Bafico, Violaine K. Harris, Stuart A. Aaronson

Institution: Icahn School of Medicine at Mount Sinai

Language: English

Topic: Wnt/β-catenin signaling in development and cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: National Cancer Institute

Awards: WNT Receptor Signaling and Cancer, G8124111166