Bone morphogenetic protein-1/Tolloid-like proteinases process dentin matrix protein-1.
Bone morphogenetic protein-1 (BMP-1)/Tolloid-like metalloproteinases play key roles in formation of mammalian extracellular matrix (ECM), through the biosynthetic conversion of precursor proteins into their mature functional forms. These proteinases probably play a further role in formation of bone through activation of transforming growth factor beta-like BMPs. Dentin matrix protein-1 (DMP1), deposited into the ECM during assembly and involved in initiating mineralization of bones and teeth, is thought to undergo proteolysis in vivo to generate functional cleavage fragments found in extracts of mineralized tissues. Here, we have generated recombinant DMP1 and demonstrate that it is cleaved, to varying extents, by all four mammalian BMP-1/Tolloid-like proteinases, to generate fragments similar in size to those previously isolated from bone. Consistent with possible roles for the BMP-1/Tolloid-like proteinases in the physiological processing of DMP1, NH2-terminal sequences of products generated by BMP-1 cleavage of DMP1 match those predicted from processing at the predicted DMP1 site that shows greatest cross-species conservation of sequences. Moreover, fibroblasts derived from mouse embryos homozygous null for genes encoding three of the four mammalian BMP-1/Tolloid-like proteinases appear to be deficient in processing of DMP1. Thus, a further role for BMP-1-Tolloid-like proteinases in formation of mineralized tissues is indicated, via proteolytic processing of DMP1.
Steiglitz
Barry M
BM
Department of Biomolecular Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Ayala
Melvin
M
Narayanan
Karthikeyan
K
George
Anne
A
Greenspan
Daniel S
DS
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism*; D011233:Precipitin Tests; D011498:Protein Precursors / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012795:Sialoglycoproteins; D014162:Transfection; D000099311:Dentin Sialophosphoprotein
D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins; D016326:Extracellular Matrix Proteins; D008666:Metalloendopeptidases; D010750:Phosphoproteins; D011498:Protein Precursors; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C513309:DMP1 protein, human; C513308:Dmp1 protein, mouse; C525705:BMP1 protein, human; C525707:Bmp1 protein, mouse