Sclerostin–erbB-3 interactions: Modulation of erbB-3 activity by sclerostin

► Sclerostin interacts with the carboxyl-terminal domain of the erbB-3 receptor. ► Sclerostin increases erbB-3 receptor signaling following treatment of cells with neuregulin/heregulin. ► Modulation of EGF/erbB signaling in bone by sclerostin is one of the mechanisms by which sclerostin controls bon...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2010-11, Vol.402 (2), p.421-424
Main Authors: Craig, Theodore A., Kumar, Rajiv
Format: Article
Language:English
Subjects:
3T3 Cells
Amino Acid Sequence
Animals
Bone Morphogenetic Proteins - genetics
Bone Morphogenetic Proteins - metabolism
Cell Line
Epidermal growth factor receptor
erbB-3
Gene Library
Genetic Markers - genetics
Humans
Mice
Molecular Sequence Data
Osteoblast
Osteoblasts - metabolism
Receptor, ErbB-3 - genetics
Receptor, ErbB-3 - metabolism
Sclerostin
Two-Hybrid System Techniques
Yeast two hybrid
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Summary:► Sclerostin interacts with the carboxyl-terminal domain of the erbB-3 receptor. ► Sclerostin increases erbB-3 receptor signaling following treatment of cells with neuregulin/heregulin. ► Modulation of EGF/erbB signaling in bone by sclerostin is one of the mechanisms by which sclerostin controls bone growth. To gain insights into the mechanism of action of sclerostin, a protein that regulates bone mass, we performed yeast two-hybrid analyses using human SOST (sclerostin) cDNA cloned into pGBKT7 DNA-binding domain vector as a bait, and a normalized, high-complexity, universal cDNA library in a GAL4 activating domain vector. We identified an interaction between sclerostin and the carboxyl-terminal portion of the receptor tyrosine-protein kinase erbB-3. To determine the biological relevance of this interaction, we treated MC3T3-E1 mouse osteoblast cells transfected with either a SOST expression plasmid or a control vector, with recombinant heregulin/neuregulin. Phospho-p44/42 (Thr202/Tyr204) MAPK was assessed in heregulin/neuregulin treated cells. We observed an increase in phospho-p44/42 (Thr202/Tyr204) MAPK concentrations in SOST transfected cells but not in cells transfected with a control vector, thus demonstrating a modulatory effect of sclerostin on heregulin/neuregulin signaling in osteoblasts. The data demonstrate that sclerostin functions in part, by modulating the activity of erbB-3.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2010.10.048