Imperial College London
Alternate

ProfessorRobertGlen

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Computational Medicine
 
 
 
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Contact

 

+44 (0)20 7594 7912r.glen Website

 
 
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Location

 

362Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tong:2019:10.1038/s41598-019-49758-x,
author = {Tong, Z and Guo, J and Glen, RC and Morrell, NW and Li, W},
doi = {10.1038/s41598-019-49758-x},
journal = {Scientific Reports},
pages = {1--9},
title = {A Bone Morphogenetic Protein (BMP)-derived peptide based on the Type I receptor-binding site modifies cell-type dependent BMP signalling},
url = {http://dx.doi.org/10.1038/s41598-019-49758-x},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Bone morphogenetic proteins (BMPs) are multifunctional cytokines of the transforming growth factor β (TGFβ) superfamily with potential therapeutic applications due to their broad biological functionality. Designing BMP mimetics with specific activity will contribute to the translational potential of BMP-based therapies. Here, we report a BMP9 peptide mimetic, P3, designed from the type I receptor binding site, which showed millimolar binding affinities for the type I receptor activin receptor like kinase 1 (ALK1), ALK2 and ALK3. Although showing no baseline activity, P3 significantly enhanced BMP9-induced Smad1/5 phosphorylation as well as ID1, BMPR2, HEY1 and HEY2 gene expression in pulmonary artery endothelial cells (hPAECs), and this activity is dependent on its alpha helix propensity. However, in human dermal microvascular endothelial cells, P3 did not affect BMP9-induced Smad1/5 phosphorylation, but potently inhibited ALK3-dependent BMP4-induced Smad1/5 phosphorylation and gene expression. In C2C12 mouse myoblast cells, P3 had no effect on BMP9-induced osteogenic signalling, which is primarily mediated by ALK2. Interestingly, a previously published peptide from the knuckle region of BMP9 was found to inhibit BMP4-induced Smad1/5 phosphorylation. Together, our data identify a BMP9-derived peptide that can selectively enhance ALK1-mediated BMP9 signalling in hPAECs and modulate BMP9 and BMP4 signalling in a cell type-specific manner.
AU  - Tong,Z
AU  - Guo,J
AU  - Glen,RC
AU  - Morrell,NW
AU  - Li,W
DO  - 10.1038/s41598-019-49758-x
EP  - 9
PY  - 2019///
SN  - 2045-2322
SP  - 1
TI  - A Bone Morphogenetic Protein (BMP)-derived peptide based on the Type I receptor-binding site modifies cell-type dependent BMP signalling
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-019-49758-x
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000486139700028&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41598-019-49758-x
UR  - http://hdl.handle.net/10044/1/75049
VL  - 9
ER  -
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