Domains and Maturation Processes That Regulate the Activity of ADAMTS-2, a Metalloproteinase Cleaving the Aminopropeptide of Fibrillar Procollagens Types I–III and V*

By A. Colige, F. Ruggiero, I. Vandenberghe, Johanne Dubail, Frédéric Kesteloot, J. V. Van Beeumen, A. Beschin, L. Brys, C. Lapière, B. Nusgens. 2005

115 citations recorded by the source corpus.

Processing of fibrillar collagens is required to generate collagen monomers able to self-assemble into elongated and cylindrical collagen fibrils. ADAMTS-2 belongs to the “A disintegrin and metalloproteinase with thrombospondin type 1 motifs” (ADAMTS) family. It is responsible for most of the processing of the aminopropeptide of type I procollagen in the skin, and it also cleaves type II and type III procollagens. ADAMTS are complex secreted enzymes that are implicated in various physiological and pathological processes. Despite accumulating evidence indicating that their activity is regulated by ancillary domains, additional information is required for a better understanding of the specific function of each domain. We have generated 17 different recombinant forms of bovine ADAMTS-2 and characterized their processing, activity, and cleavage specificity. The results indicated the following: (i) activation of the ADAMTS-2 zymogen involves several cleavages, by proprotein convertases and C-terminal processing, and generates at least seven distinct processed forms; (ii) the C-terminal domain negatively regulates enzyme activity, whereas two thrombospondin type 1 repeats are enhancer regulators; (iii) the 104-kDa form displays the highest aminoprocollagen peptidase activity on procollagen type I; (iv) ADAMTS-2 processes the aminopropeptide of α1 type V procollagen homotrimer at the end of the variable domain; and (v) the cleaved sequence (PA) is different from the previously described sites ((P/A)Q) for ADAMTS-2, redefining its cleavage specificity. This finding and the existence of multiple processed forms of ADAMTS-2 strongly suggest that ADAMTS-2 may be involved in function(s) other than processing of fibrillar procollagen types I–III.

Subfields: Cancer Research, Genetics, Immunology and Allergy

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The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. R. Khalil
2. S. Zhong
3. Hideaki Nagase
4. M. Bekhouche
5. A. Colige
6. Gillian Murphy

In Genetics

1. S. Zhong
2. R. Khalil

In Immunology and Allergy

1. S. Zhong
2. R. Khalil
3. M. Bekhouche
4. A. Colige

Citations in the corpus

• A Disintegrin and Metalloproteinase (ADAM) and ADAM with Thrombospondin Motifs (ADAMTS) Family in Vascular Biology and Disease (2019, background): “Studies on ADAMTS-2 have shown that an autocatalytic cleavage occurring within the C-terminal end, possibly in the procollagen N-propetidase domain, increases its activity [35, 41].”
• Extracellular matrix structure. (2016, unknown): “23 forming tropocollagen triple helix [139, 147].”
• Loss of ADAMTS3 activity causes Hennekam lymphangiectasia–lymphedema syndrome 3 (2017, methodology): “Similar to ADAMTS2 (18), the activity of ADAMTS3 is largely regulated by several proteolytic processes (Supplementary Material, Fig.”
• The procollagen N-proteinases ADAMTS2, 3 and 14 in pathophysiology. (2015, background): “However, it was later shown that recombinant ADAMTS2 is also the main enzyme responsible for the processing of the aminopropeptide of type III procollagen [17,19,25] and that the cleavage site is identical to that of type I and type II procollagens (Fig.”
• ADAMTS-2 functions as anti-angiogenic and anti-tumoral molecule independently of its catalytic activity (2010, methodology): “However, its molecular size is different since a functional catalytic pocket is required for the autocatalytic processing of PNP terminal domain [19].”
• Collagens at a glance (2007, background): “The N-propeptides are cleaved by procollagen N-proteinases, which are identical to the ADAMTS 2, ADAMTS 3 and ADAMTS 14 proteinases (Colige et al., 2005).”
• The C-terminal domains of ADAMTS-4 and ADAMTS-5 promote association with N-TIMP-3 (2009, background): “, 2008) and C-terminal domains of ADAMTS-2 modulate processing of the N-terminal propeptide of procollagen (Colige et al., 2005).”