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Control of type IV collagenase activity by components of the urokinase–plasmin system: a regulatory mechanism with cell‐bound reactants
Author(s) -
Mazzieri Roberta,
Masiero Laura,
Zanetta Lucia,
Monea Sara,
Onisto Maurizio,
Garbisa Spiridione,
Mignatti Paolo
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.9.2319
Subject(s) - biology , plasmin , collagenase , mechanism (biology) , microbiology and biotechnology , biochemistry , urokinase , genetics , enzyme , philosophy , epistemology
The urokinase‐type plasminogen activator (uPA) and the matrix‐degrading metalloproteinases MMP‐2 and MMP‐9 (type IV collagenases/gelatinases) have been implicated in a variety of invasive processes, including tumor invasion, metastasis and angiogenesis. MMP‐2 and MMP‐9 are secreted in the form of inactive zymogens that are activated extracellularly, a fundamental process for the control of their activity. The physiological mechanism(s) of gelatinase activation are still poorly understood; their comprehension may provide tools to control cell invasion. The data reported in this paper show multiple roles of the uPA–plasmin system in the control of gelatinase activity: (i) both gelatinases are associated with the cell surface; binding of uPA and plasmin(ogen) to the cell surface results in gelatinase activation without the action of other metallo‐ or acid proteinases; (ii) inhibition of uPA or plasminogen binding to the cell surface blocks gelatinase activation; (iii) in soluble phase plasmin degrades both gelatinases; and (iv) gelatinase activation and degradation occur in a dose‐ and time‐dependent manner in the presence of physiological plasminogen and uPA concentrations. Thus, the uPA–plasmin system may represent a physiological mechanism for the control of gelatinase activity.