Procollagen II Amino Propeptide Processing by ADAMTS-3
By Russell J. Fernandes, S. Hirohata, J. M. Engle, A. Colige, Daniel H. Cohn, David R. Eyre, S. Apte. 2001
230 citations recorded by the source corpus.
The amino and carboxyl propeptides of procollagens I and II are removed by specific enzymes as a prerequisite for fibril assembly. Null mutations in procollagen I N-propeptidase (ADAMTS-2) cause dermatosparaxis in cattle and the Ehlers-Danlos syndrome (dermatosparactic type) in humans by preventing proteolytic excision of the N-propeptide of procollagen I. We have found that procollagen II is processed normally in dermatosparactic nasal cartilage, suggesting the existence of another N-propeptidase(s). We investigated such a role for ADAMTS-3 in Swarm rat chondrosarcoma RCS-LTC cells, which fail to process the procollagen II N-propeptide. Stable transfection of RCS-LTC cells with bovine ADAMTS-2 or human ADAMTS-3 partially rescued the processing defect, suggesting that ADAMTS-3 has procollagen II N-propeptidase activity. Human skin and skin fibroblasts showed 30-fold higher mRNA levels of ADAMTS-2 than ADAMTS-3, whereas ADAMTS-3 mRNA was 5-fold higher than ADAMTS-2 mRNA in human cartilage. We propose that both ADAMTS-2 and ADAMTS-3 process procollagen II, but ADAMTS-3 is physiologically more relevant, given its preferred expression in cartilage. The findings provide an explanation for the sparing of cartilage in dermatosparaxis and, perhaps, for the relative sparing of some procollagen I-containing tissues.
Subfields: Cell Biology, Immunology and Allergy, Rheumatology
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cell Biology
In Immunology and Allergy
In Rheumatology
Citations in the corpus
- A Disintegrin and Metalloproteinase (ADAM) and ADAM with Thrombospondin Motifs (ADAMTS) Family in Vascular Biology and Disease (2019, background): “The role of ADAMTS-2, 3, and 14 as procollagen N-endopeptidases was demonstrated in 2001 [11, 12].”
- A Disintegrin and Metalloproteinase with Thrombospondin Motifs 18 Deficiency Leads to Visceral Adiposity and Associated Metabolic Syndrome in Mice. (2017, background): “8 e 10 The functions of ADAMTSs include N-terminal procollagen processing (ADAMTSs 2, 3, and 14) 11 e 14 ; spermatogenesis (ADAMTS2) 15 ; follicular rupture and ovulation (ADAMTS1) 16 ; angiogenesis inhibition (ADAMTSs 1, 8, and 9) 17,18 ; degradation of cartilage oligomeric matrix protein (ADAMTSs…”
- CCBE1 Enhances Lymphangiogenesis via A Disintegrin and Metalloprotease With Thrombospondin Motifs-3–Mediated Vascular Endothelial Growth Factor-C Activation (2014, background): “The cleavage motif of ADAMTS3 in VEGF-C is the same as the ADAMTS2 motif in procollagens (FA[AP]↓),45 which have been until now the only known substrates of ADAMTS3.”
- Biochemistry and physiological functions of ADAMTS7 metalloprotease (2013, background): “Three specific functions have emerged through the characterization of several ADAMTS members, and they include the processing of procollagen by ADAMTS2 [4, 5], the degradation of chondroitin sulfate proteoglycans by ADAMTS4 [6-8] or ADAMTS5 [9-12], and the cleavage of von Willebrand factor (VWF) by ”
- ADAMTS proteins in human disorders (2018, background): “Indeed, ADAMTS3 was previously shown to cleave the Npropeptide of procollagen II, a major component of cartilage ECM where it is strongly expressed during development [35, 36].”
- Secreted Metalloproteinase ADAMTS-3 Inactivates Reelin (2017, result): “The reported characteristics of ADAMTS-3 (Fernandes et al., 2001; Apte, 2009), including zinc dependency, a requirement for proprotein convertase activity for maturation, molecular weight, and heparin binding, were consistent with those of the protease that mediates N-t cleavage (Hisanaga et…”