A Bone Morphogenetic Protein (BMP)-derived Peptide Based on the Type I Receptor-binding Site Modifies Cell-type Dependent BMP Signalling.

ABSTRACT: 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.

SUBMITTER: Tong Z 

PROVIDER: S-EPMC6748948 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature