Tissue inhibitor of metalloproteinases-2 inhibits the activation of 72 kDa progelatinase by fibroblast membranes.
We report that monolayers of human fibroblasts stimulated with concanavalin A were able to activate 72 kDa progelatinase but not 95 kDa progelatinase. The activating capacity of fibroblasts appeared approx. 6 h after concanavalin A stimulation and was blocked by cycloheximide. The activation of 72 kDa progelatinase was readily inhibited by TIMP-2 but only poorly by TIMP-1. Plasma membranes isolated from the fibroblasts were capable of activating 72 kDa progelatinase. The cleavage products of the plasma membrane-mediated activation of 72 kDa progelatinase corresponded to those of organomercurial-induced self-cleavage. Only inhibitors of metalloproteinase self-cleavage inhibited the activating capacity of plasma membrane preparations, although the activating capacity was destroyed by trypsin and heat. As with the fibroblast monolayers, TIMP-2 was a potent inhibitor of the membrane-mediated activation whereas TIMP-1 was less so.
Ward
R V
RV
Cell and Molecular Biology Department, Strangeways Research Laboratory, Cambridge, U.K.
Atkinson
S J
SJ
Slocombe
P M
PM
Docherty
A J
AJ
Reynolds
J J
JJ
Murphy
G
G
D001665:Binding Sites; D002462:Cell Membrane / Q000187:drug effects* / Q000201:enzymology; D003208:Concanavalin A; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors*; D005347:Fibroblasts / Q000187:drug effects; D018093:Gelatinases; D006358:Hot Temperature; D008666:Metalloendopeptidases; D009363:Neoplasm Proteins / Q000378:metabolism / Q000494:pharmacology*; D010434:Pepsin A / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D019716:Tissue Inhibitor of Metalloproteinase-2; D014357:Trypsin
D004792:Enzyme Precursors; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D003208:Concanavalin A; D019716:Tissue Inhibitor of Metalloproteinase-2; D003513:Cycloheximide; D014357:Trypsin; D010434:Pepsin A; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase