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J Biol Chem. 2016 Dec 2;291(49):25716-25728. Epub 2016 Oct 26.

Altering the Proteoglycan State of Transforming Growth Factor β Type III Receptor (TβRIII)/Betaglycan Modulates Canonical Wnt/β-Catenin Signaling.

Author information

1
From the Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208.
2
the Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus, Ohio 43210.
3
From the Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, mythreye@sc.edu.
4
the Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, South Carolina 29208, and.

Abstract

Hyperactive Wnt/β-catenin signaling is linked to cancer progression and developmental abnormalities, making identification of mechanisms controlling Wnt/β-catenin signaling vital. Transforming growth factor β type III receptor (TβRIII/betaglycan) is a transmembrane proteoglycan co-receptor that exists with or without heparan and/or chondroitin sulfate glycosaminoglycan (GAG) modifications in cells and has established roles in development and cancer. Our studies here demonstrate that TβRIII, independent of its TGFβ co-receptor function, regulates canonical Wnt3a signaling by controlling Wnt3a availability through its sulfated GAG chains. Our findings revealed, for the first time, opposing functions for the different GAG modifications on TβRIII suggesting that Wnt interactions with the TβRIII heparan sulfate chains result in inhibition of Wnt signaling, likely via Wnt sequestration, whereas the chondroitin sulfate GAG chains on TβRIII promote Wnt3a signaling. These studies identify a novel, dual role for TβRIII/betaglycan and define a key requirement for the balance between chondroitin sulfate and heparan sulfate chains in dictating ligand responses with implications for both development and cancer.

KEYWORDS:

TBRIII; Wnt signaling; betaglycan; cancer biology; cell signaling; glycosaminoglycan; transforming growth factor β (TGF-β)

PMID:
27784788
PMCID:
PMC5207267
DOI:
10.1074/jbc.M116.748624
[Indexed for MEDLINE]
Free PMC Article

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