Oxidative Autoactivation of Latent Collagenase by Human Neutrophils

Weiss, Stephen J.; Peppin, Gary J.; Ortiz, X.; Ragsdale, Carol Godoshian; Test, Samuel T.

doi:10.1126/science.2982211

Cited by 440 publications

(218 citation statements)

References 19 publications

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“…Until recently, MMPs were thought to undergo activation extracellularly after either oxidative or proteolytic perturbation of propeptide domain-catalytic domain interactions (Weiss et al, 1985;Nagase and Woessner, 1999). However, a precedent for intracellular processing was established when the stromelysin-3 zymogen was reported to undergo constitutive activation (Pei and Weiss, 1995;Santavicca et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Membrane Type-1 Matrix Metalloproteinase Activation by Proprotein Convertases

Yana

Weiss

2000

MBoC

278

271

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Membrane type-1 matrix metalloproteinase (MT1-MMP) is the prototypical member of a subgroup of membrane-anchored proteinases that belong to the matrix metalloproteinase family. Although synthesized as a zymogen, MT1-MMP plays an essential role in extracellular matrix remodeling after an undefined process that unmasks its catalytic domain. We now report the existence of a proprotein convertase-MT1-MMP axis that regulates the processing and functional activity of the metalloproteinase. Two sets of basic motifs in the propeptide region of MT1-MMP are identified that potentially can be recognized by the proprotein convertase family of subtilisinlike proteases. Processing of proMT1-MMP as well as the expression of its proteolytic activity were blocked by mutating these recognition motifs or by inhibiting the proprotein convertases furin and PC6 with the serpin-based inhibitor ␣ 1 antitrypsin Portland. Furthermore, both furindependent and furin-independent MT1-MMP processing pathways are identified that require tethering of the metalloproteinase to the cell surface. These findings demonstrate the existence of a proprotein convertase-MT1-MMP axis that can regulate extracellular matrix remodeling.

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Section: Discussionmentioning

confidence: 99%

Regulation of Membrane Type-1 Matrix Metalloproteinase Activation by Proprotein Convertases

Yana

Weiss

2000

MBoC

278

271

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“…In vitro, a number of proMMPs are activated by reactive oxygen species (ROS), which can modify the cysteine thiol group and activate proMMPs via autolytic cleavage. For example, hypochlorous acid (HOCl), a product of neutrophil myeloperoxidase (MPO), and hydroxyl radicals activate proMMPs-1, -7, and -9 (Fu et al, 2001;Michaelis et al, 1992;Peppin and Weiss, 1986;Weiss et al, 1985), and peroxynitrate can activate proMMPs-1, -2, and -9 (Okamoto et al, 1997). However, a role for most ROS as in vivo activators of MMPs has not been established.…”

Section: Oxidative Control Of Mmp Activitymentioning

confidence: 99%

Control of matrix metalloproteinase catalytic activity

2007

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SummaryAs their name implies, MMPs were first described as proteases that degrade extracellular matrix proteins, such as collagens, elastin, proteoglycans, and laminins. However, studies of MMP function in vivo have revealed that these proteinases act on a variety of extracellular protein substrates, often to activate latent forms of effector proteins, such as antimicrobial peptides and cytokines, or to alter protein function, such as shedding of cell-surface proteins. Because their substrates are diverse, MMPs are involved in variety of homeostatic functions, such as bone remodeling, wound healing, and several aspects of immunity. However, MMPs are also involved in a number of pathological processes, such as tumor progression, fibrosis, chronic inflammation, tissue destruction, and more. A key step in regulating MMP proteolysis is the conversion of the zymogen into an active proteinase. Several proMMPs are activated in the secretion pathway by furin proprotein convertases, but for most the activation mechanisms are largely not known. In this review, we discuss both authentic and potential mechanisms of proMMP activation.

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“…The occurrence of Phe79 at the Nterminus of the neutrophil collagenase seemed to be critical for superactivation, which is in agreement with data published by Suzuki, Enghild, Morodomi, Salvesen and Nagase [(1990) (Knauper et al, 1990a). In addition, it was demonstrated that neutrophil procollagenase is activated by oxygen radicals, which are generated during the respiratory burst of neutrophils (Weiss et al, 1985;Burkhardt et al, 1986;Saari et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Direct activation of human neutrophil procollagenase by recombinant stromelysin

Knäuper

Wilhelm

Seperack

et al. 1993

Biochemical Journal

149

105

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Human neutrophil procollagenase was activated by incubation with recombinant active stromelysin. Activation was achieved by cleavage of the Gly78-Phe79 peptide bond at the end of the propeptide domain in a single-step activation mechanism. In addition, accelerated activation was achieved when N-terminally truncated, latent collagenase (with Phe49 as its N-terminal residue) was incubated with recombinant active stromelysin. Determination of the specific activity of recombinant-stromelysin-activated neutrophil collagenase with dinitrophenyl-octapeptide or type I collagen demonstrated the generation of high specific activity. The specific activity of stromelysin-activated enzyme was considerably higher than that of trypsin- or HgCl2-activated collagenase. Thus human neutrophil collagenase is superactivated, like the homologous fibroblast collagenase [Murphy, Cockett, Stephens, Smith and Docherty (1987) Biochem. J. 248, 265-268]. The occurrence of Phe79 at the N-terminus of the neutrophil collagenase seemed to be critical for superactivation, which is in agreement with data published by Suzuki, Enghild, Morodomi, Salvesen and Nagase [(1990) Biochemistry 29, 10261-10270] on fibroblast collagenase.

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Oxidative Autoactivation of Latent Collagenase by Human Neutrophils

Cited by 440 publications

References 19 publications

Regulation of Membrane Type-1 Matrix Metalloproteinase Activation by Proprotein Convertases

Regulation of Membrane Type-1 Matrix Metalloproteinase Activation by Proprotein Convertases

Control of matrix metalloproteinase catalytic activity

Direct activation of human neutrophil procollagenase by recombinant stromelysin

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