Altering the proteoglycan state of TβRIII/Betaglycan modulates canonical Wnt/β-catenin signaling (original) (raw)
The Journal of biological chemistry, 2016
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 can exist with or without heparan and/or chondroitin sulfate glycosaminoglycan (GAG) modifications in cells, with 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 reveal, for the first time, opposing functions for the different GAG modifications on TβRIII and suggest that Wnt interactions with TβRIIIs heparan sulfate chains result in inhibition of Wnt signaling, likely via Wnt sequestration, while the chondroitin sulfate GAG chains on TβRIII can promote Wnt3a signaling. These studies identify a n...
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