TY - JOUR
T1 - Sclerostin-erbB-3 interactions
T2 - Modulation of erbB-3 activity by sclerostin
AU - Craig, Theodore A.
AU - Kumar, Rajiv
N1 - Funding Information:
Supported by NIH grant DK 76829 and a grant from the Dr. Ralph and Marian C. Falk Medical Research Trust (RK).
PY - 2010/11/12
Y1 - 2010/11/12
N2 - 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.
AB - 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.
KW - Epidermal growth factor receptor
KW - ErbB-3
KW - Osteoblast
KW - Sclerostin
KW - Yeast two hybrid
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UR - http://www.scopus.com/inward/citedby.url?scp=78149447051&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2010.10.048
DO - 10.1016/j.bbrc.2010.10.048
M3 - Article
C2 - 20951118
AN - SCOPUS:78149447051
SN - 0006-291X
VL - 402
SP - 421
EP - 424
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -