RGD Reference Report - Betaglycan can act as a dual modulator of TGF-beta access to signaling receptors: mapping of ligand binding and GAG attachment sites. - Rat Genome Database

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Betaglycan can act as a dual modulator of TGF-beta access to signaling receptors: mapping of ligand binding and GAG attachment sites.

Authors: Lopez-Casillas, F  Payne, HM  Andres, JL  Massague, J 
Citation: Lopez-Casillas F, etal., J Cell Biol. 1994 Feb;124(4):557-68.
RGD ID: 1579949
Pubmed: (View Article at PubMed) PMID:8106553

Betaglycan, also known as the TGF-beta type III receptor, is a membrane-anchored proteoglycan that presents TGF-beta to the type II signaling receptor, a transmembrane serine/threonine kinase. The betaglycan extracellular region, which can be shed by cells into the medium, contains a NH2-terminal domain related to endoglin and a COOH-terminal domain related to uromodulin, sperm receptors Zp2 and 3, and pancreatic secretory granule GP-2 protein. We identified residues Ser535 and Ser546 in the uromodulin-related region as the glycosaminoglycan (GAG) attachment sites. Their mutation to alanine prevents GAG attachment but does not interfere with betaglycan stability or ability to bind and present TGF-beta to receptor II. Using a panel of deletion mutants, we found that TGF-beta binds to the NH2-terminal endoglin-related region of betaglycan. The remainder of the extracellular domain and the cytoplasmic domain are not required for presentation of TGF-beta to receptor II; however, membrane anchorage is required. Soluble betaglycan can bind TGF-beta but does not enhance binding to membrane receptors. In fact, recombinant soluble betaglycan acts as potent inhibitor of TGF-beta binding to membrane receptors and blocks TGF-beta action, this effect being particularly pronounced with the TGF-beta 2 isoform. The results suggest that release of betaglycan into the medium converts this enhancer of TGF-beta action into a TGF-beta antagonist.

Annotation

Gene Ontology Annotations    

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Tgfb1  (transforming growth factor, beta 1)
Tgfb2  (transforming growth factor, beta 2)
Tgfbr2  (transforming growth factor, beta receptor 2)
Tgfbr3  (transforming growth factor beta receptor 3)


Additional Information