Bone Morphogenetic Protein 1 Prodomain Specifically Binds and Regulates Signaling by Bone Morphogenetic Proteins 2 and 4

Jasuja, Reema; Ge, Gaoxiang; Voss, Nikolas G.; Lyman-Gingerich, Jamie; Branam, Amanda M.; Pelegri, Francisco; Greenspan, Daniel S.

doi:10.1074/jbc.m610929200

Cited by 32 publications

(25 citation statements)

References 42 publications

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“…At the molecular level, the BMP signal pathway was reported to be critical for calcification and bone formation. 8,[11][12][13]26 The BMP family has at least 30 members, among which BMPs-1-7, which were initially isolated from deminer- alized bone matrix, are capable of inducing ectopic bone formation. 8 BMP-1 is a kind of metalloproteinase with conserved domains, and can convert a variety of precursor proteins into mature or active forms that are involved in extracellular matrix formation.…”

Section: Discussionmentioning

confidence: 99%

Survival impact of psammoma body, stromal calcification, and bone formation in papillary thyroid carcinoma

et al. 2009

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The presence of calcification is the most significant ultrasonographic finding in evaluating thyroid nodules. Calcifications are more frequently detected in papillary thyroid carcinoma than in other thyroid lesions. However, the clinical significance of calcification, including clinical correlations and impact on survival, and the molecular mechanism responsible for calcification in papillary thyroid carcinoma remain uncertain. We performed a retrospective study of patients with primary common-type papillary thyroid carcinoma to determine the clinical correlations of calcification and its impact on survival. Histologically, calcification was classified as either psammoma bodies, stromal calcification, or bone formation. They were identified in 25, 47, and 13% of all 229 cases of papillary thyroid carcinoma, respectively. The presence of psammoma bodies was significantly correlated with gross lymph node metastasis and stage grouping. Both stromal calcification and bone formation were significantly correlated with patient age. In addition, stromal calcification was associated with pT classification and gross lymph node metastasis. Papillary thyroid carcinoma with, compared to that without, psammoma bodies was associated with poorer disease-free survival. We examined the quantitative expression of BMP-1, a metalloproteinase that is reported to be involved in bone and extracellular matrix formations, and found that its expression was significantly higher in tumors with psammoma bodies or with stromal calcification (P ¼ 0.0464 and 0.0272, respectively). These results suggest that the presence of psammoma bodies is a useful predictor of outcome for patients suffering from papillary thyroid carcinoma.

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Section: Discussionmentioning

confidence: 99%

Survival impact of psammoma body, stromal calcification, and bone formation in papillary thyroid carcinoma

et al. 2009

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“…The prodomain confers latency and is cleaved in the Golgi of some cell types by subtilisin-like proprotein convertases (SPCs) (10), whereas in other cell types, B/TPs are secreted with prodomains intact (11,12), suggesting extracellular activation. In Drosophila embryos, most TLD occurs as a prodomain-retaining form, suggesting an activation limited by either inefficient or regulated processing (4).…”

Section: B/tp Structurementioning

confidence: 99%

“…In Drosophila embryos, most TLD occurs as a prodomain-retaining form, suggesting an activation limited by either inefficient or regulated processing (4). BMP1/mTLD prodomain sequences, which co-purify with TGF␤-like BMPs from osteoinductive bone extracts (1), can bind BMP2 and BMP4 with high affinity and may participate in regulating their activity in vivo (12).…”

Section: B/tp Structurementioning

confidence: 99%

Metalloproteinases in Drosophila to Humans That Are Central Players in Developmental Processes

Muir

Greenspan

2011

Journal of Biological Chemistry

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Many secreted proteins are synthesized as precursors with propeptides that must be cleaved to yield the mature functional form of the molecule. In addition, various growth factors occur in extracellular latent complexes with protein antagonists and are activated upon cleavage of such antagonists. Research in the separate fields of embryonic patterning and extracellular matrix formation has identified members of the BMP1/Tolloid-like family of metalloproteinases as key players in these types of biosynthetic processing events in species ranging from Drosophila to humans. Bone morphogenic proteins (BMPs)2 were first defined by the ability to induce de novo bone formation and were first identified in bone extracts (1). Although all other BMPs are members of the TGF␤ superfamily of growth factors, BMP1 is a metalloproteinase, the first demonstrated role of which was as a procollagen C-proteinase (pCP) (2) that cleaves C-propeptides from procollagen precursors to produce mature monomers of the major fibrillar collagens I-III. This activity is crucial to bone biology, as collagen I is the major protein component of bone and is essential to bone structure/function. After initial cloning of mammalian BMP1, Tolloid (TLD), the protein product of a zygotically active gene involved in dorsoventral patterning of Drosophila embryos, was shown to have a domain structure resembling that of BMP1 (3) and was later shown to exert patterning effects by activating the TGF␤-like BMP decapentaplegic (DPP) (4). Subsequently, BMP1 and TLD have become prototypes of the BMP1/TLD-like proteinase (B/TP) family. B/TPs in a broad range of species are now implicated in processes that include extracellular matrix (ECM) formation and mineralization, embryonic patterning, growth factor activation, and generation of anti-angiogenic protein fragments, all via cleavage of a growing list of substrates.

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“…The prodomains are not required for secretion of at least some BMP1/TLD-like proteinases (Marques et al, 1997;Sieron et al, 2000), but are required for maintaining latency (Marques et al, 1997;Sieron et al, 2000;Leighton and Kadler, 2003). The prodomains appear to be proteolytically removed via subtilisin-like proprotein convertases (SPCs), within the trans-Golgi compartments of some cells (Leighton and Kadler, 2003), although some cell types secrete BMP1/TLD-like proteinase as unprocessed forms Jasuja et al, 2007). CUB domains are thought to mediate protein-protein interactions (Bork and Beckmann, 1993).…”

Section: Bmp1/tld Family Membersmentioning

confidence: 99%

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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Bone Morphogenetic Protein 1 Prodomain Specifically Binds and Regulates Signaling by Bone Morphogenetic Proteins 2 and 4

Cited by 32 publications

References 42 publications

Survival impact of psammoma body, stromal calcification, and bone formation in papillary thyroid carcinoma

Survival impact of psammoma body, stromal calcification, and bone formation in papillary thyroid carcinoma

Metalloproteinases in Drosophila to Humans That Are Central Players in Developmental Processes

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

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