Partial Purification and Characterization of a Procollagen C-Proteinase from the Culture Medium of Mouse Fibroblasts

Kessler, Efrat; Adar, R; Goldberg, Burton; Niece, Ronald L.

doi:10.1016/s0174-173x(86)80010-3

Cited by 56 publications

(31 citation statements)

References 37 publications

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“…Nonetheless, small amounts of residual pCP activity in mouse embryos doubly null for the genes which encode BMP1, mTLD and mTLL1, suggest that mTLL2 may be an in vivo pCP . BMP1/TLD-like proteinases are secreted molecules, pCP activity has a pH optimum of 8.0 -8.5 (Hojima et al, 1985;Kessler et al, 1986), and various studies have demonstrated both pCP activity and unprocessed procollagen in the extracellular space in cell and organ cultures. However, it has recently been reported that processing of procollagen C-propeptides of the major fibrillar collagens occurs intracellularly, under presumably acidic conditions, in developing tendon (Canty et al, 2004).…”

Section: Fibrillar Collagensmentioning

confidence: 99%

“…1). Cleavage of both N-and C-propeptides occurs via highly specific calciumdependent metalloproteinases with neutral pH optima (Hojima et al, 1985;Kessler et al, 1986), and is necessary for releasing the mature triple helical portion of the molecule for proper self-assembly into fibrils (Myllyharju and Kivirikko, 2001;Canty and Kadler, 2005) Disintegrin And Metalloproteinase with ThromboSpondin repeats) family (Greenspan and Wang, 2005); specifically via the structurally similar proteinases ADAMTS2, 3 and 14, which have overlapping but differing distributions in tissues (Colige et al, 1997;Le Goff et al, 2006;Wang et al, 2003). Deficiencies in N-propeptide processing leads to the arthrochalasis and dermatosparaxis forms of Ehlers-Danlos Syndrome (EDS) (Byers, 1995).…”

Section: Introductionmentioning

confidence: 99%

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The bone morphogenetic protein 1/Tolloid-like metalloproteinases

2007

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A decade ago, bone morphogenetic protein 1 (BMP1) was shown to provide the activity necessary for proteolytic removal of the C-propeptides of procollagens I-III: precursors of the major fibrillar collagens. Subsequent studies have shown BMP1 to be the prototype of a small group of extracellular metalloproteinases that play manifold roles in regulating formation of the extracellular matrix (ECM). Soon after initial cloning of BMP1, genetic studies showed the related Drosophila proteinase Tolloid (TLD) to be necessary for formation of the dorsal-ventral axis in early embryogenesis. It is now clear that the BMP1/TLD-like proteinases, conserved in species ranging from Drosophila to humans, act in dorsal-ventral patterning via activation of transforming growth factor β (TGFβ)-like proteins BMP2, BMP4 (vertebrates) and decapentaplegic (arthropods). More recently, it has become apparent that the BMP1/TLD-like proteinases are key activators of a broader subset of the TGFβ superfamily of proteins, with implications that these proteinases may be key in orchestrating formation of ECM with growth factor activation and BMP signaling in morphogenetic processes.

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Section: Fibrillar Collagensmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

2007

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“…5). All the single mutants (panel A, lanes [3][4][5][6]8, and 9) and the double CUB1 mutant (panel B, lane 2) were secreted. The N4Q and N6Q mutants were not secreted (see lanes 10 and 11).…”

Section: N-linked Oligosaccharides Are Necessary For Proper Folding Amentioning

confidence: 99%

“…BMP-1, mammalian tolloid, and two highly homologous relatives tolloid-like 1 and 2 constitute the tolloid clade of astacin-like metalloproteinases that have important functions in development and extracellular matrix formation (2). BMP-1 cleaves fibrillar procollagen type I, II, III (3,4), and V (5-7), as well as type VII procollagen (8), prolysyl oxidase (9), probiglycan (10), and the ␥2 chain of prolaminin 5 (11). BMP-1 also cleaves chordin (2) therefore affecting dorsal-ventral patterning in vertebrates (12).…”

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confidence: 99%

Post-translational Modification of Bone Morphogenetic Protein-1 Is Required for Secretion and Stability of the Protein

Garrigue‐Antar

Hartigan

Kadler

2002

Journal of Biological Chemistry

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Bone morphogenetic protein (BMP)-1 is a glycosylated metalloproteinase that is fundamental to the synthesis of a normal extracellular matrix because it cleaves type I procollagen, as well as other precursor proteins. Sequence analysis suggests that BMP-1 has six potential N-linked glycosylation sites (i.e. NXS/T) namely: Asn 91 (prodomain), Asn 142 (metalloproteinase domain), Asn 332 and Asn 363 (CUB1 domain), Asn 599 (CUB3 domain), and Asn 726 in the C-terminal-specific domain. In this study we showed that all these sites are N-glycosylated with complex-type oligosaccharides containing sialic acid, except Asn 726 presumably because proline occurs immediately C-terminal of threonine in the consensus sequence. Recombinant BMP-1 molecules lacking all glycosylation sites or the three CUB-specific sites were not secreted. BMP-1 lacking CUB glycosylation was translocated to the proteasome for degradation. BMP-1 molecules lacking individual glycosylation sites were efficiently secreted and exhibited full procollagen C-proteinase activity, but N332Q and N599Q exhibited a slower rate of cleavage. BMP-1 molecules lacking any one of the CUB-specific glycosylation sites were sensitive to thermal denaturation. The study showed that the glycosylation sites in the CUB domains of BMP-1 are important for secretion and stability of the molecule.Bone morphogenetic protein-1 (BMP-1), 1 also known as procollagen C-proteinase-1 (PCP-1) was first identified in osteogenic extracts of bone (1). BMP-1 is a smaller splice variant of mammalian tolloid, which is the vertebrate ortholog of tolloid, in Drosophila. BMP-1, mammalian tolloid, and two highly homologous relatives tolloid-like 1 and 2 constitute the tolloid clade of astacin-like metalloproteinases that have important functions in development and extracellular matrix formation (2). BMP-1 cleaves fibrillar procollagen type I, II, III (3, 4), and V (5-7), as well as type VII procollagen (8), prolysyl oxidase (9), probiglycan (10), and the ␥2 chain of prolaminin 5 (11). BMP-1 also cleaves chordin (2) therefore affecting dorsal-ventral patterning in vertebrates (12). Similarly, tolloid cleaves the chordin homologue short gastrulation during Drosophila embryo development (13). Bmp1 homozygous null mice are perinatal lethal, with defects in ventral body wall closure and collagen fibrillogenesis (14), which illustrates the importance of BMP-1 in tissue assembly and development.BMP-1 consists of a prodomain that is cleaved by a furin-like enzyme in the trans-Golgi network, 2 an astacin-like zinc metalloproteinase domain (15), one epidermal growth factor-like domain, and three CUB domains. In other proteins, CUB domains mediate protein-protein interactions (16).BMP-1 purified from mouse fibroblasts culture medium has been shown to be N-glycosylated (17). Sequence analysis reveals six potential N-glycosylation sites, one of which is located in the prodomain and five in the mature (active) molecule. However, no information is available on the structure and function of the glycosylation sites....

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“…The tolloids are a subfamily of the metzincins, which includes bone morphogenetic protein (BMP)-1, 2 mammalian tolloid (mTLD, a product of alternatively spliced mRNA encoded by the same gene that encodes BMP-1 (16)), and mammalian tolloid-like (mTLL)-1 and -2 (17,18). BMP-1 and mTLD exhibit procollagen C-proteinase activity in that they cleave the C-propeptides from procollagens I-III (19,20). BMP-1 also cleaves C-and N-propeptides from different chains of procollagen V (5-7), the prodomains of probiglycan (8) and prolysyl oxidase (21,22), chordin (18), and the ␣3 and ␥2 chains of laminin 5 (9,10), thus controlling collagen fibril polymerization (23,24), proteoglycan maturation, cross-linking of collagens and elastin, dorso-ventral patterning (18,25), and assembly of the dermal-epidermal junction (26).…”

mentioning

confidence: 99%

Proteinases of the Bone Morphogenetic Protein-1 Family Convert Procollagen VII to Mature Anchoring Fibril Collagen

Rattenholl¹,

Pappano²,

Koch³

et al. 2002

Journal of Biological Chemistry

109

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Collagen VII is the major structural component of the anchoring fibrils at the dermal-epidermal junction in the skin. It is secreted by keratinocytes as a precursor, procollagen VII, and processed into mature collagen during polymerization of the anchoring fibrils. We show that bone morphogenetic protein-1 (BMP-1), which exhibits procollagen C-proteinase activity, cleaves the Cterminal propeptide from human procollagen VII. The cleavage occurs at the BMP-1 consensus cleavage site SYAA2DTAG within the NC-2 domain. Mammalian tolloid-like (mTLL)-1 and -2, two other proteases of the astacin enzyme family, were able to process procollagen VII at the same site in vitro. Immunohistochemical and genetic evidence supported the involvement of these enzymes in cleaving type VII procollagen in vivo. Both BMP-1 and mTLL-1 are expressed in the skin and in cultured cutaneous cells. A naturally occurring deletion in the human COL7A1 gene, 8523del14, which is associated with dystrophic epidermolysis bullosa and eliminates the BMP-1 consensus sequence, abolished processing of procollagen VII, and in mutant skin procollagen VII accumulated at the dermal-epidermal junction. On the other hand, deficiency of BMP-1 in the skin of knockout mouse embryos did not prevent processing of procollagen VII to mature collagen, suggesting that mTLL-1 and/or mTLL-2 can substitute for BMP-1 in the processing of procollagen VII in situ.

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Partial Purification and Characterization of a Procollagen C-Proteinase from the Culture Medium of Mouse Fibroblasts

Cited by 56 publications

References 37 publications

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

Post-translational Modification of Bone Morphogenetic Protein-1 Is Required for Secretion and Stability of the Protein

Proteinases of the Bone Morphogenetic Protein-1 Family Convert Procollagen VII to Mature Anchoring Fibril Collagen

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