A core domain of the BMP2 proregion is sufficient for the biogenesis of mature homodimeric growth factor

Abstract

The large proregions of cystine knot growth factors exert several important biological functions. Previous results have shown that the proregion of BMP2 retards the activity of the mature growth factor. Hitherto, no information exists about the function of the BMP2 proregion during the biogenesis of the mature growth factor. Here, evidence is presented that the proregion is required for the secretion of BMP2 when present in covalent linkage to the mature domain. In trans complementation, i.e., with the proregion encoded by a separate plasmid, does not result in secretion of homodimeric mature growth factor. An extended variant of a previously in vitro characterized subdomain of the proregion, when being present in covalent linkage to the mature growth factor, restores secretion of mature BMP2, albeit at a reduced level.

Cystine knot growth factors and their functionally versatile proregions

“…In case of BMP4, the proregion of BMP2 improved the yield of recombinant BMP4 in the cell culture supernatant (Hammonds et al, 1991). Likewise, deletion of the proregion of BMP2 resulted in a secretion defect of recombinant BMP2 (Kuhfahl and Schwarz, 2015). In contrast to the results obtained for TGF-β1 or Act A, secretion of BMP2 required covalent linkage with the proregion and no trans complementation was observed (Gray and Mason, 1990;Kuhfahl and Schwarz, 2015).…”

Continuous release of bone morphogenetic protein-2 through nano-graphene oxide-based delivery influences the activation of the NF-κB signal transduction pathway

“…Therefore, a significant feature for the suitability of these biomaterials is the ability to provide controlled release of the biologically active molecules. 36 Based on the literature, we analyzed the main reasons that GO could potentially serve as an excellent carrier of small molecule drugs, which can be summarized as follows: first, GO has a single or bilayer atomic layer structure. Good hydrophilicity allows its complete dispersal in water.…”