RGD Reference Report - Noggin and sclerostin bone morphogenetic protein antagonists form a mutually inhibitory complex. - Rat Genome Database

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Noggin and sclerostin bone morphogenetic protein antagonists form a mutually inhibitory complex.

Authors: Winkler, DG  Yu, C  Geoghegan, JC  Ojala, EW  Skonier, JE  Shpektor, D  Sutherland, MK  Latham, JA 
Citation: Winkler DG, etal., J Biol Chem. 2004 Aug 27;279(35):36293-8. Epub 2004 Jun 14.
RGD ID: 1599074
Pubmed: PMID:15199066   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M400521200   (Journal Full-text)

Noggin and sclerostin are bone morphogenetic protein (BMP) antagonists that modulate mitogenic activity through sequestering BMPs. Little is known of the interactions among this class of proteins. We show that recombinant sclerostin and noggin bound to each other with high affinity (K(D) = 2.92 nm). This observation has been extended to naturally expressed noggin and sclerostin from the rat osteosarcoma cell line, ROS 17/2.8, supporting a role for the complex in natural systems. The noggin-sclerostin complex was competitive with BMP binding and mutually attenuated the activity of each BMP antagonist. Collectively, the data demonstrate a novel and exquisite paradigm for the regulation of BMP activity through direct neutralization of the BMP and activation by co-localized BMP antagonist expression. The pleiotrophic nature of noggin and sclerostin represents a novel mechanism for the fine-tuning of BMP activity in bone homeostasis.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ossification  IEP 1599074 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
extracellular space  IDA 1599074; 1599074 RGD 
protein-containing complex  IDA 1599074; 1599074 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IPISost (Rattus norvegicus)1599074 RGD 
protein binding  IPINog (Rattus norvegicus)1599074 RGD 
protein-containing complex binding  IDA 1599074 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nog  (noggin)
Sost  (sclerostin)


Additional Information