Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein.
The actions of human recombinant stromelysins-1 and -2, collagenase, gelatinases A and B and matrilysin on neonatal human proteoglycan aggregates were examined. With the exception of gelatinase B, aggrecan was degraded extensively by most metalloproteinases studied, whereas link protein showed only limited proteolysis. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Cleavage at the former bond generated a link protein component with the same N-terminus as that isolated from newborn human cartilage. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.
Nguyen
Q
Q
Strangeways Research Laboratory, Warts Causeway, Cambridge, U.K.
Murphy
G
G
Hughes
C E
CE
Mort
J S
JS
Roughley
P J
PJ
D053674:Aggrecans; D000595:Amino Acid Sequence; D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology; D005109:Extracellular Matrix / Q000201:enzymology*; D016326:Extracellular Matrix Proteins; D006801:Humans; D006868:Hydrolysis; D007231:Infant, Newborn; D037181:Lectins, C-Type; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000276:immunology / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D011994:Recombinant Proteins; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured; D000099249:Proteoglycan Link Protein
D053674:Aggrecans; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D008666:Metalloendopeptidases; D011506:Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; D000099249:Proteoglycan Link Protein; C508320:Acan protein, mouse