Activity and inhibition of prostasin and matriptase on apical and basolateral surfaces of human airway epithelial cells

Nimishakavi, Shilpa; Besprozvannaya, Marina; Raymond, Wilfred W.; Craik, Charles S.; Gruenert, Dieter C.; Caughey, George H.

doi:10.1152/ajplung.00303.2011

Cited by 17 publications

(24 citation statements)

References 40 publications

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“…As shown in Fig. 4A, this substrate is selective for mouse marapsin over mouse prostasin, whereas commercially available substrate QAR-4NA (which is a substrate for human prostasin and detects prostasin and matriptase activity in cultured cells (31)) was preferred by mouse prostasin.…”

Section: A Tetrapeptide Substrate Based On Marapsin Cleavage Preferenmentioning

confidence: 97%

Mutational Tail Loss Is an Evolutionary Mechanism for Liberating Marapsins and Other Type I Serine Proteases from Transmembrane Anchors

Raman

Trivedi

Raymond

et al. 2013

Journal of Biological Chemistry

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Background: Vertebrate marapsins can be either type I transmembrane proteases or unanchored. Results: Point mutations liberated marapsins from transmembrane peptides independently in human-related primates and other mammalian clades. Soluble marapsins are active and inhibitor-resistant. Conclusion: Mutational tail loss transformed transmembrane marapsins and related proteins into soluble proteases. Significance: These findings suggest a general evolutionary mechanism for evolving proteases with new properties and functions.

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Section: A Tetrapeptide Substrate Based On Marapsin Cleavage Preferenmentioning

confidence: 97%

Mutational Tail Loss Is an Evolutionary Mechanism for Liberating Marapsins and Other Type I Serine Proteases from Transmembrane Anchors

Raman

Trivedi

Raymond

et al. 2013

Journal of Biological Chemistry

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“…Indeed, a point mutation introduced in the catalytic triad confirmed that the proteolytic activation of HAT requires serine protease activity in transfected human embryonic kidney cells 293 (HEK293 cells) (60). Whether HAT can activate other TTSPs is still underexplored, but this is highly likely since activation of family members has been described for other members of the family (99,116).…”

Section: Hat: Structure Catalytic Activity and Regulationmentioning

confidence: 99%

Human airway trypsin-like protease, a serine protease involved in respiratory diseases

Menou

Duitman

Flajolet

et al. 2017

American Journal of Physiology-Lung Cellular and Molecular Phys

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More than 2% of all human genes are coding for a complex system of more than 700 proteases and protease inhibitors. Among them, serine proteases play extraordinary, diverse functions in different physiological and pathological processes. The human airway trypsin-like protease (HAT), also referred to as TMPRSS11D and serine 11D, belongs to the emerging family of cell surface proteolytic enzymes, the type II transmembrane serine proteases (TTSPs). Through the cleavage of its four major identified substrates, HAT triggers specific responses, notably in epithelial cells, within the pericellular and extracellular environment, including notably inflammatory cytokine production, inflammatory cell recruitment, or anticoagulant processes. This review summarizes the potential role of this recently described protease in mediating cell surface proteolytic events, to highlight the structural features, proteolytic activity, and regulation, including the expression profile of HAT, and discuss its possible roles in respiratory physiology and disease.

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“…Serine proteinases expressed by epithelial cells (prostasin 58 ) or PMNs (NE 59 ), and acidic proteinases expressed by macrophages and epithelial cells (cathepsins B and S 60,61 ) proteolytically activate airway ENaC to increase sodium hyperabsorption and ASL dehydration. However, to date, there are no reports in the literature that MMPs proteolytically regulate ENaC or other sodium channels in the airway epithelium.…”

Section: Cftr and Mmpsmentioning

confidence: 99%

Matrix metalloproteinases in cystic fibrosis: pathophysiologic and therapeutic perspectives

Owen

Jojas-Quintero²

2016

MNM

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Cystic fibrosis (CF) is the most common inherited disease in the Caucasian population. CF is caused by loss-of-function mutations in the CFTR gene leading to an altered electrolyte and water movement into the airway surface liquid, dehydration of the mucus layer, defective mucociliary clearance, and increased susceptibility to airway bacterial infections. CF is characterized by airway neutrophilic inflammation and activation of airway epithelial cells leading to increased airway levels of various matrix metalloproteinases (MMPs). Herein, we review MMP structure, regulation, and activity, along with the literature on MMPs expression in CF and the contributions of MMPs to CF pathogenesis. Numerous studies report elevated levels of MMPs (especially MMP-8, MMP-7, and MMP-9) in blood and/or lung samples from CF patients and have correlated MMP levels with measures of lung inflammation and injury and/or clinical parameters. No study has yet investigated the contributions of MMPs to the pathogenesis of CF using MMP gene-targeted murine of CF. Based upon the known activities of MMPs in animal models of other lung diseases, we hypothesize that some MMPs (such as MMP-8 and MMP-9) may amplify airway inflammation, and promote airway injury and airway-remodeling processes, or inhibit chloride epithelial transport by inhibiting activation of the CFTR (MMP-2). Other MMPs (such as MMP-7 and MMP-12) may limit the severity of CF by activating host defense proteins to enhance pathogen clearance from the airways, directly killing pathogens that colonize the airways of CF patients and/or promoting epithelial repair. We discuss potential approaches to selectively target MMPs to develop novel therapies that limit the high morbidity and mortality associated with CF.

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Activity and inhibition of prostasin and matriptase on apical and basolateral surfaces of human airway epithelial cells

Abstract: Nimishakavi S, Besprozvannaya M, Raymond WW, Craik CS, Gruenert DC, Caughey GH. Activity and inhibition of prostasin and matriptase on apical and basolateral surfaces of human airway epithelial cells.

Cited by 17 publications

References 40 publications

Mutational Tail Loss Is an Evolutionary Mechanism for Liberating Marapsins and Other Type I Serine Proteases from Transmembrane Anchors

Mutational Tail Loss Is an Evolutionary Mechanism for Liberating Marapsins and Other Type I Serine Proteases from Transmembrane Anchors

Human airway trypsin-like protease, a serine protease involved in respiratory diseases

Matrix metalloproteinases in cystic fibrosis: pathophysiologic and therapeutic perspectives

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