title: Bone morphogenetic protein 1 prodomain specifically binds and regulates signaling by bone morphogenetic proteins 2 and 4.
abstract: Highly purified fractions of bone extracts capable of inducing ectopic bone formation have been reported to contain peptides corresponding to the mature active regions of the TGF-beta-like bone morphogenetic proteins (BMPs) 2-7, and to the prodomain region of the metalloproteinase BMP1. Co-purification of BMPs 2-7 with BMP1 prodomain sequences through the multiple biochemical steps used in these previous reports has suggested the possibility of interactions between the BMP1 prodomain and BMPs 2-7. Here we demonstrate that the BMP1 prodomain binds BMPs 2 and 4 with high specificity and with a KD of approximately 11 nM, in the physiological range. It is further demonstrated that the BMP1 prodomain is capable of modulating signaling by BMPs 2 and 4 in vitro and in vivo, and that endogenous BMP1 prodomain-BMP4 complexes exist in cell culture media and in tissues.
authors.affiliation: Program in Molecular and Cellular Pharmacology, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Reema
authors.initials: R
authors.lastname: Jasuja
authors.forename: Gaoxiang
authors.initials: G
authors.lastname: Ge
authors.forename: Nikolas G
authors.initials: NG
authors.lastname: Voss
authors.forename: Jamie
authors.initials: J
authors.lastname: Lyman-Gingerich
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Branam
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Pelegri
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Greenspan
mesh_terms: D000818:Animals; D055395:Bone Morphogenetic Protein 1; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008666:Metalloendopeptidases / Q000737:chemistry*; D009693:Nucleic Acid Hybridization; D010006:Osteoblasts / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D020349:Surface Plasmon Resonance; D016212:Transforming Growth Factor beta / Q000737:chemistry*; D015027:Zebrafish; D029961:Zebrafish Proteins
chemical_list: C525718:BMP2 protein, human; C525809:BMP4 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; C525813:bmp4 protein, zebrafish; D008666:Metalloendopeptidases; C525705:BMP1 protein, human; D055395:Bone Morphogenetic Protein 1