Activation of human progelatinase A by collagenase and matrilysin: activation of procollagenase by matrilysin.
Proteolytic and nonproteolytic methods were used to investigate the mechanism(s) by which human fibroblast progelatinase A and fibroblast-type procollagenase can be activated. Both collagenase and matrilysin were able to activate progelatinase A, resulting in an amino terminus in gelatinase A of Tyr81. The cleavage occurred distal to Cys73 within the sequence of PRCGNPDVAN80-Y81NFFPRKP. While several nonproteolytic reagents were tested, only the heavy metal Hg(II) and p-chloromercuribenzoate (PCMB) were able to induce activation of progelatinase A and resulted in the conversion of the latent 72-kDa gelatinase A to an active form of about 64.5 kDa. Matrilysin was also able to activate procollagenase and resulted in an amino terminus in collagenase of Phe81. These results suggest that fibroblast-type collagenase and matrilysin may be physiologically relevant activators of progelatinase A; the maintenance of latency and the process of activation for progelatinase A may occur through the cysteine-switch mechanism, and the proteolytic activation of procollagenase by matrilysin resulted in the same amino terminus as produced by stromelysin-1.
Sang
Q A
QA
Department of Chemistry, Florida State University, Tallahassee 32306-3006, USA.
Bodden
M K
MK
Windsor
L J
LJ
D000595:Amino Acid Sequence; D000818:Animals; D017364:Collagenases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000502:physiology; D004792:Enzyme Precursors / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology; D018093:Gelatinases / Q000737:chemistry / Q000378:metabolism*; D005881:Gingiva / Q000166:cytology; D006801:Humans; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D051381:Rats; D017421:Sequence Analysis; D016622:Silver Staining; D013997:Time Factors
D004792:Enzyme Precursors; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; C022440:procollagenase; C069860:progelatinase; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7