scholarly journals Systemic Injection of CK2.3, a Novel Peptide Acting Downstream of Bone Morphogenetic Protein Receptor BMPRIa, Leads to Increased Trabecular Bone Mass

2014 ◽  
Vol 33 (2) ◽  
pp. 208-215 ◽  
Author(s):  
Hemanth Akkiraju ◽  
Jeremy Bonor ◽  
Kristine Olli ◽  
Chris Bowen ◽  
Beth Bragdon ◽  
...  
2012 ◽  
Vol 227 (7) ◽  
pp. 2870-2879 ◽  
Author(s):  
Beth Bragdon ◽  
Jeremy Bonor ◽  
Kathryn L. Shultz ◽  
Wesley G. Beamer ◽  
Clifford J. Rosen ◽  
...  

Bone ◽  
2012 ◽  
Vol 50 (1) ◽  
pp. 189-199 ◽  
Author(s):  
Beth Bragdon ◽  
Alex D'Angelo ◽  
Lauren Gurski ◽  
Jeremy Bonor ◽  
Kathryn L. Schultz ◽  
...  

2010 ◽  
Vol 285 (48) ◽  
pp. 37641-37649 ◽  
Author(s):  
Hannah J. Durrington ◽  
Paul D. Upton ◽  
Simon Hoer ◽  
Jessica Boname ◽  
Benjamin J. Dunmore ◽  
...  

2020 ◽  
Vol 13 (9) ◽  
pp. dmm045971 ◽  
Author(s):  
Jelmer Hoeksma ◽  
Gerard C. M. van der Zon ◽  
Peter ten Dijke ◽  
Jeroen den Hertog

ABSTRACTZebrafish models are well-established tools for investigating the underlying mechanisms of diseases. Here, we identified cercosporamide, a metabolite from the fungus Ascochyta aquiliqiae, as a potent bone morphogenetic protein receptor (BMPR) type I kinase inhibitor through a zebrafish embryo phenotypic screen. The developmental defects in zebrafish, including lack of the ventral fin, induced by cercosporamide were strikingly similar to the phenotypes caused by renowned small-molecule BMPR type I kinase inhibitors and inactivating mutations in zebrafish BMPRs. In mammalian cell-based assays, cercosporamide blocked BMP/SMAD-dependent transcriptional reporter activity and BMP-induced SMAD1/5-phosphorylation. Biochemical assays with a panel of purified recombinant kinases demonstrated that cercosporamide directly inhibited kinase activity of type I BMPRs [also called activin receptor-like kinases (ALKs)]. In mammalian cells, cercosporamide selectively inhibited constitutively active BMPR type I-induced SMAD1/5 phosphorylation. Importantly, cercosporamide rescued the developmental defects caused by constitutively active Alk2 in zebrafish embryos. We believe that cercosporamide could be the first of a new class of molecules with potential to be developed further for clinical use against diseases that are causally linked to overactivation of BMPR signaling, including fibrodysplasia ossificans progressiva and diffuse intrinsic pontine glioma.This article has an associated First Person interview with the first author of the paper.


2018 ◽  
Vol 114 (suppl_1) ◽  
pp. S97-S97
Author(s):  
S Sharma ◽  
A Alimohammadi ◽  
S Chausheva ◽  
J Altmann ◽  
A Panzenboeck ◽  
...  

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