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PMID:12927798

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Citation

Irie, A, Habuchi, H, Kimata, K and Sanai, Y (2003) Heparan sulfate is required for bone morphogenetic protein-7 signaling. Biochem. Biophys. Res. Commun. 308:858-65

Abstract

Although genetic studies have suggested that heparan sulfate (HS) is involved in bone morphogenetic protein (BMP)-mediated embryonic morphogenesis, it is unclear whether HS is directly involved in BMP-mediated signaling. Here, we investigate the involvement of HS in BMP-7 signaling. We show that HS and heparin chains specifically bind to BMP-7. Digestion of cell-surface HS with heparitinase interferes with BMP-7-mediated Smad phosphorylation in ROS 17/2.8 osteoblastic cells. Inhibiting sulfation of cell-surface HS with chlorate also causes interruption of Smad phosphorylation. Addition of exogenous heparin to ROS 17/2.8 cells prevents BMP-7-mediated Smad phosphorylation rather than enhances the BMP-7 signal, suggesting that HS should be anchored on the plasma membrane for BMP signaling. Moreover, BMP-7 binding to ROS 17/2.8 cells is inhibited by chlorate treatment and exogenous application of heparin. These results demonstrate that BMP-7 specifically binds to cell-surface HS and the BMP-7-HS interaction is required for BMP-7 signaling.

Links

PubMed

Keywords

Animals; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins/metabolism; Cell Membrane/enzymology; Cell Membrane/metabolism; Chlorine/pharmacology; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Glycosaminoglycans/metabolism; Heparin/metabolism; Heparitin Sulfate/metabolism; Immunoblotting; Models, Chemical; Osteoblasts; Phosphorylation; Polysaccharide-Lyases/metabolism; Protein Binding; Rats; Reverse Transcriptase Polymerase Chain Reaction; Sepharose/metabolism; Signal Transduction; Transforming Growth Factor beta; Tumor Cells, Cultured

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:G3V6W8

involved_in

GO:0030509: BMP signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

RAT:G3V6W8

enables

GO:0008201: heparin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:G3V6W8

involved_in

GO:0042325: regulation of phosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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