Mutation of a cleavage site adjacent to the mature domain leads to increase in secreted mature BMP-2 with reduced activity

References

• Beckwith J. 2000. The all purpose gene fusion. Methods Enzymol. 326:3–7.
   PubMedGoogle Scholar
• Bergeron F, Leduc R, Day R. 2000. Subtilase-like pro-protein convertases: From molecular specificity to therapeutic applications. J Mol Endocrinol. 24:1–22.
   PubMed Web of Science ®Google Scholar
• Chen D, Zhao M, Mundy GR. 2004. Bone morphogenetic proteins. Growth Factors. 22:233–241.
   PubMed Web of Science ®Google Scholar
• Constam DB, Robertson EJ. 1999. Regulation of bone morphogenetic protein activity by pro domains and proprotein convertases. J Cell Biol. 144:139–149.
   PubMed Web of Science ®Google Scholar
• Cui Y, Hackenmiller R, Berg L, Jean F, Nakayama T, Thomas G, Christian JL. 2001. The activity and signaling range of mature BMP-4 is regulated by sequential cleavage at two sites within the prodomain of the precursor. Genes Dev. 15:2797–2802.
   PubMedGoogle Scholar
• Cui Y, Jean F, Thomas G, Christian JL. 1998. BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development. EMBO J. 17:4735–4743.
   PubMed Web of Science ®Google Scholar
• Degnin C, Jean F, Thomas G, Christian JL. 2004. Cleavages within the prodomain direct intracellular trafficking and degradation of mature bone morphogenetic protein-4. Mol Biol Cell. 15:5012–5020.
   PubMedGoogle Scholar
• Dick A, Hild M, Bauer H, Imai Y, Maifeld H, Schier AF, Talbot WS, Bouwmeester T, Hammerschmidt M. 2000. Essential role of Bmp7 (snailhouse) and its prodomain in dorsoventral patterning of the zebrafish embryo. Development. 127:343–354.
   PubMedGoogle Scholar
• Gasteiger E, Gattiker A, Hoogland C, Ivanyi I, Appel RD, Bairoch A. 2003. ExPASy: The proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res. 31:3784–3788.
   PubMed Web of Science ®Google Scholar
• Goldman DC, Hackenmiller R, Nakayama T, Sopory S, Wong C, Kulessa H, Christian JL. 2006. Mutation of an upstream cleavage site in the BMP4 prodomain leads to tissue-specific loss of activity. Development. 133:1933–1942.
   PubMed Web of Science ®Google Scholar
• Govender S, Csimma C, Genant HK, Valentin-Opran A, Amit Y, Arbel R, Aro H, Atar D, Bishay M, Borner MG, Chiron P, Choong P, Cinats J, Courtenay B, Feibel R, Geulette B, Gravel C, Haas N, Raschke M, Hammacher E, van der Velde D, Hardy P, Holt M, Josten C, Ketterl RL, Lindeque B, Lob G, Mathevon H, McCoy G, Marsh D, Miller R, Munting E, Oevre S, Nordsletten L, Patel A, Pohl A, Rennie W, Reynders P, Rommens PM, Rondia J, Rossouw WC, Daneel PJ, Ruff S, Ruter A, Santavirta S, Schildhauer TA, Gekle C, Schnettler R, Segal D, Seiler H, Snowdowne RB, Stapert J, Taglang G, Verdonk R, Vogels L, Weckbach A, Wentzensen A, Wisniewski T. 2002. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: A prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am. 84:2123–2134.
   PubMed Web of Science ®Google Scholar
• Harrison CA, Al-Musawi SL, Walton KL. 2011. Prodomains regulate the synthesis, extracellular localisation and activity of TGF-beta superfamily ligands. Growth Factors. 29:174–186.
   PubMed Web of Science ®Google Scholar
• Hauburger A, von Einem S, Schwaerzer GK, Buttstedt A, Zebisch M, Schraml M, Hortschansky P, Knaus P, Schwarz E. 2009. The pro-form of BMP-2 interferes with BMP-2 signalling by competing with BMP-2 for IA receptor binding. FEBS J. 276:6386–6398.
   PubMed Web of Science ®Google Scholar
• Huang Y, Li Y, Wang YG, Gu X, Wang Y, Shen BF. 2007. An efficient and targeted gene integration system for high-level antibody expression. J Immunol Methods. 322:28–39.
   PubMed Web of Science ®Google Scholar
• Israel DI, Nove J, Kerns KM, Moutsatsos IK, Kaufman RJ. 1992. Expression and characterization of bone morphogenetic protein-2 in Chinese hamster ovary cells. Growth Factors. 7:139–150.
   PubMed Web of Science ®Google Scholar
• Jesty J, Nemerson Y. 1976. The activation of bovine coagulation factor X. Methods Enzymol. 45:95–107.
   PubMedGoogle Scholar
• Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N, Ikeda T, Rosen V, Wozney JM, Fujisawa-Sehara A, Suda T. 1994. Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol. 127:1755–1766.
   PubMed Web of Science ®Google Scholar
• Lu H, Khurana S, Verma N, Manischewitz J, King L, Beigel JH, Golding H. 2011. A rapid Flp-In system for expression of secreted H5N1 influenza hemagglutinin vaccine immunogen in mammalian cells. PLoS One. 6:e17297.
   PubMedGoogle Scholar
• Nelsen SM, Christian JL. 2009. Site-specific cleavage of BMP4 by furin, PC6, and PC7. J Biol Chem. 284:27157–27166.
   PubMedGoogle Scholar
• Peel SA, Hu ZM, Clokie CM. 2003. In search of the ideal bone morphogenetic protein delivery system: In vitro studies on demineralized bone matrix, purified, and recombinant bone morphogenetic protein. J Craniofac Surg. 14:284–291.
   PubMedGoogle Scholar
• Roe S, Francullo LE, Paradis TM, Porter TJ, Leonard M, Charlebois T. 2004. Effects of posttranslational processing on rhBMP-2 cellular productivity and product quality. BioProcess Int. 3:32–43.
   Google Scholar
• Sopory S, Kwon S, Wehrli M, Christian JL. 2010. Regulation of Dpp activity by tissue-specific cleavage of an upstream site within the prodomain. Dev Biol. 346:102–112.
   PubMedGoogle Scholar
• Sopory S, Nelsen SM, Degnin C, Wong C, Christian JL. 2006. Regulation of bone morphogenetic protein-4 activity by sequence elements within the prodomain. J Biol Chem. 281:34021–34031.
   PubMed Web of Science ®Google Scholar
• Suzuki A, Kaneko E, Ueno N, Hemmati-Brivanlou A. 1997. Regulation of epidermal induction by BMP2 and BMP7 signaling. Dev Biol. 189:112–122.
   PubMed Web of Science ®Google Scholar
• von Einem S, Schwarz E, Rudolph R. 2010. A novel TWO-STEP renaturation procedure for efficient production of recombinant BMP-2. Protein Expr Purif. 73:65–69.
   PubMed Web of Science ®Google Scholar
• von Einem S, Erler S, Bigl K, Frerich B, Schwarz E. 2011. The pro-form of BMP-2 exhibits a delayed and reduced activity when compared to mature BMP-2. Growth Factors. 29:63–71.
   PubMed Web of Science ®Google Scholar
• Wiberg FC, Rasmussen SK, Frandsen TP, Rasmussen LK, Tengbjerg K, Coljee VW, Sharon J, Yang CY, Bregenholt S, Nielsen LS, Haurum JS, Tolstrup AB. 2006. Production of target-specific recombinant human polyclonal antibodies in mammalian cells. Biotechnol Bioeng. 94:396–405.
   PubMed Web of Science ®Google Scholar
• Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA. 1988. Novel regulators of bone formation: Molecular clones and activities. Science. 242:1528–1534.
   PubMed Web of Science ®Google Scholar