A matrix metalloproteinase proenzyme activator produced by articular cartilage.

Autor: Towle CA; Orthopaedic Research Laboratories, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, 02114, USA., Wright M, Hecht AC, Kuong SJ, Papanicolas LE, Totkovic R, Mankin HJ, Treadwell BV
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 1998 Jun 18; Vol. 247 (2), pp. 324-31.
DOI: 10.1006/bbrc.1998.8781
Abstrakt: Matrix metalloproteinases (MMPs) are involved in connective tissue turnover under physiological and pathological conditions. MMP activity is regulated by the requirement for zymogen activation. This report describes a proMMP-3 activator produced by articular cartilage. The activator initiates a step-wise processing of proMMP-3 to generate an array of active species. Sequencing of activation intermediates demonstrated cleavage on the NH2-terminal side of certain basic residues in the MMP-3 propeptide. Metal ion chelators inhibited activator-dependent proteolysis, and activity was restored by low levels of ZnCl2. These catalytic properties suggest similarity to members of the insulinase superfamily of metalloendopeptidases with in vitro specificity for single arginine or paired basic processing sites in a variety of prohormones. Dibasic sites also exist in the propeptides of several MMPs including proMMP-3. This is the first report that cartilage produces a potent MMP proenzyme activator, opening the possibility of a novel intrinsic activation pathway for catabolic processes in this avascular tissue.
(Copyright 1998 Academic Press.)
Databáze: MEDLINE
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