Bone morphogenetic protein-1 processes probiglycan.
Bone morphogenetic protein-1 (BMP-1) is a metalloprotease that plays important roles in regulating the deposition of fibrous extracellular matrix in vertebrates, including provision of the procollagen C-proteinase activity that processes the major fibrillar collagens I-III. Biglycan, a small leucine-rich proteoglycan, is a nonfibrillar extracellular matrix component with functions that include the positive regulation of bone formation. Biglycan is synthesized as a precursor with an NH(2)-terminal propeptide that is cleaved to yield the mature form found in vertebrate tissues. Here, we show that BMP-1 cleaves probiglycan at a single site, removing the propeptide and producing a biglycan molecule with an NH(2) terminus identical to that of the mature form found in tissues. BMP-1-related proteases mammalian Tolloid and mammalian Tolloid-like 1 (mTLL-1) are shown to have low but detectable levels of probiglycan-cleaving activity. Comparison shows that wild type mouse embryo fibroblasts (MEFs) produce only fully processed biglycan, whereas MEFs derived from embryos homozygous null for the Bmp1 gene, which encodes both BMP-1 and mammalian Tolloid, produce predominantly unprocessed probiglycan, and MEFs homozygous null for both the Bmp1 gene and the mTLL-1 gene Tll1 produce only unprocessed probiglycan. Thus, all detectable probiglycan-processing activity in MEFs is accounted for by the products of these two genes.
Scott
I C
IC
Departments of Pathology and Laboratory Medicine and Biomolecular Chemistry University of Wisconsin, Madison, Wisconsin 53706, USA.
Imamura
Y
Y
Pappano
W N
WN
Troedel
J M
JM
Recklies
A D
AD
Roughley
P J
PJ
Greenspan
D S
DS
D000818:Animals; D058578:Biglycan; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D058575:Decorin; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D006720:Homozygote; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D045726:Metalloproteases; D051379:Mice; D008817:Mice, Mutant Strains; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D055394:Tolloid-Like Metalloproteinases
C546884:BGN protein, human; C546885:Bgn protein, mouse; D058578:Biglycan; D019485:Bone Morphogenetic Proteins; C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011498:Protein Precursors; D011506:Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; D045726:Metalloproteases; D055394:Tolloid-Like Metalloproteinases; D008666:Metalloendopeptidases; C484478:TLL1 protein, human; C484477:Tll1 protein, mouse; C525705:BMP1 protein, human; C525707:Bmp1 protein, mouse; D055395:Bone Morphogenetic Protein 1