RGD Reference Report - Heparan sulfate is required for bone morphogenetic protein-7 signaling. - Rat Genome Database

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Heparan sulfate is required for bone morphogenetic protein-7 signaling.

Authors: Irie, A  Habuchi, H  Kimata, K  Sanai, Y 
Citation: Irie A, etal., Biochem Biophys Res Commun 2003 Sep 5;308(4):858-65.
RGD ID: 737843
Pubmed: PMID:12927798   (View Abstract at PubMed)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
BMP signaling pathway  TAS 737843 RGD 
regulation of phosphorylation  IMP 737843 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
heparin binding  IDA 737843 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bmp7  (bone morphogenetic protein 7)


Additional Information