Cloning and Characterization of the cDNA for Human Airway Trypsin-like Protease

Yamaoka, Kaoru; Masuda, Kenichi; Ogawa, Hirohisa; Takagi, Kenichiro; Umemoto, Naoji; Yasuoka, Susumu

doi:10.1074/jbc.273.19.11895

Cited by 103 publications

(108 citation statements)

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“…3A), and they were all located in the same orientation relative to transcription. One gene encoded the murine orthologue of HAT-1 (11,50). ESTs and predicted partial or complete cDNA sequences have been reported previously for the five remaining genes under the 2 S. M. Réhault, manuscript in preparation.…”

Section: Identification Of the Mouse Desc1 Gene Within A Gene Clustermentioning

confidence: 99%

Mouse DESC1 Is Located within a Cluster of Seven DESC1-like Genes and Encodes a Type II Transmembrane Serine Protease That Forms Serpin Inhibitory Complexes

Hobson

Netzel‐Arnett

Szabo

et al. 2004

Journal of Biological Chemistry

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We report the identification and functional analysis of a type II transmembrane serine protease encoded by the mouse differentially expressed in squamous cell carcinoma (DESC) 1 gene, and the definition of a cluster of seven homologous DESC1-like genes within a 0.5-Mb region of mouse chromosome 5E1. This locus is syntenic to a region of human chromosome 4q13.3 containing the human orthologues of four of the mouse DESC1-like genes. Bioinformatic analysis indicated that all seven DESC1-like genes encode functional proteases. Direct cDNA cloning showed that mouse DESC1 encodes a multidomain serine protease with an N-terminal signal anchor, a SEA (sea urchin sperm protein, enterokinase, and agrin) domain, and a C-terminal serine protease domain. The mouse DESC1 mRNA was present in epidermal, oral, and male reproductive tissues and directed the translation of a membrane-associated 60-kDa N-glycosylated protein with type II topology. Mouse DESC1 was synthesized in insect cells as a zymogen that could be activated by exposure to trypsin. The purified activated DESC1 hydrolyzed synthetic peptide substrates, showing a preference for Arg in the P 1 position. DESC1 proteolytic activity was abolished by generic inhibitors of serine proteases but not by other classes of protease inhibitors. Most interestingly, DESC1 formed stable inhibitory complexes with both plasminogen activator inhibitor-1 and protein C inhibitor that are expressed in the same tissues with DESC1, suggesting that type II transmembrane serine proteases may be novel targets for serpin inhibition. Together, these data show that mouse DESC1 encodes a functional cell surface serine protease that may have important functions in the epidermis, oral, and reproductive epithelium.Pericellular proteolysis is essential to all aspects of vertebrate life, including development, tissue homeostasis, tissue remodeling, tissue repair, and reproduction, and dysregulated pericellular proteolysis is causally related to a large number of diseases in humans. Within the past century, the most extensive studies of pericellular proteolysis in health and disease focused on defining the contribution of a relatively limited number of proteases belonging to the families of plasminogen activators, matrix metalloproteinases, and cathepsins (1-6). However, the recent completion of the mouse and human genome sequences, and the generation of extensive mouse and human EST 1 data bases, facilitated an explosion in the discovery of novel candidate protease genes, indicating that a vastly larger repertoire of pericellular proteases may be engaged in these processes than previously anticipated (7,8). Particularly noteworthy in this context was the unveiling of an unexpectedly large family of type II transmembrane serine proteases (TTSPs) (9 -23). This rapidly expanding family of serine proteases is defined by the presence of an N-terminal signal anchor and a C-terminal serine protease domain, separated by a stem region containing an array of protein domains that varies widely between individual...

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Section: Identification Of the Mouse Desc1 Gene Within A Gene Clustermentioning

confidence: 99%

Mouse DESC1 Is Located within a Cluster of Seven DESC1-like Genes and Encodes a Type II Transmembrane Serine Protease That Forms Serpin Inhibitory Complexes

Hobson

Netzel‐Arnett

Szabo

et al. 2004

Journal of Biological Chemistry

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“…Other membrane-type serine proteases involved in proteolytic cascades are enteropeptidase (4), which activates trypsinogen in the gut for digestion, and hepsin (46), which has been shown to activate factor VIIa in a blood coagulation cascade (47). Other membrane-type serine proteases include TMPRSS2 (48), human airway trypsin-like protease (49), and corin (50). Membrane-type serine proteases as signaling molecules that play key regulatory roles may become more prevalent as these novel proteases are further characterized.…”

Section: Characterization Of Mt-sp1 and Identification Of Substratesmentioning

confidence: 99%

Cellular Localization of Membrane-type Serine Protease 1 and Identification of Protease-activated Receptor-2 and Single-chain Urokinase-type Plasminogen Activator as Substrates

Takeuchi¹,

Harris²,

Huang³

et al. 2000

Journal of Biological Chemistry

399

369

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Membrane-type serine protease 1 (MT-SP1) was recently cloned, and we now report its biochemical characterization. MT-SP1 is predicted to be a type II transmembrane protein with an extracellular protease domain. This localization was experimentally verified using immunofluorescent microscopy and a cell-surface biotinylation technique. The substrate specificity of MT-SP1 was determined using a positional scanning-synthetic combinatorial library and substrate phage techniques. The preferred cleavage sequences were found to be (P4-(Arg/Lys)P3-(X)P2-(Ser)P1-(Arg)P1-(Ala)) and (P4-(X)P3-(Arg/Lys)P2-(Ser)P1(Arg) P1(Ala)), where X is a non-basic amino acid. Protease-activated receptor 2 (PAR2) and single-chain urokinase-type plasminogen activator are proteins that are localized to the extracellular surface and contain the preferred MT-SP1 cleavage sequence. The ability of MT-SP1 to activate PARs was assessed by exposing PAR-expressing Xenopus oocytes to the soluble MT-SP1 protease domain. The latter triggered calcium signaling in PAR2-expressing oocytes at 10 nM but failed to trigger calcium signaling in oocytes expressing PAR1, PAR3, or PAR4 at 100 nM. Singlechain urokinase-type plasminogen activator was activated using catalytic amounts of MT-SP1 (1 nM), but plasminogen was not cleaved under similar conditions. The membrane localization of MT-SP1 and its affinity for these key extracellular substrates suggests a role of the proteolytic activity in regulatory events.

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“…This study has allowed isolation of a differentially expressed novel gene named DESC1. DESC1 possesses strong identity to members of the serine protease superfamily, and shows highest degree of homology with Human Airway Trypsin-like protease (HAT; Yamaoka et al, 1998).…”

mentioning

confidence: 99%

Differential expression of a novel serine protease homologue in squamous cell carcinoma of the head and neck

Lang

Schuller

2001

Br J Cancer

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Summary Differential gene expression between squamous cell carcinoma of the head and neck and matched normal tissue was studied by utilizing Representational Difference Analysis. Using this methodology, a novel gene, DESC1 was isolated. DESC1 possesses strong identity to the serine protease super-family. Comparison of DESC1 expression between primary squamous cell carcinoma and matched normal tissue shows that the level of DESC1 expression is reduced or absent in 11/12 SCC tissue specimens when compared to specimens of matched normal tissue. Tissue-specific expression studies further show that DESC1 expression can only be detected in tissues derived from the head and neck, and in skin, prostate and testes. Cell line studies demonstrate that DESC1 expression is epithelial-specific. Chromosomal localization studies indicate that DESC1 is located on the long arm of chromosome 4 at position q12-13.

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Cloning and Characterization of the cDNA for Human Airway Trypsin-like Protease

Cited by 103 publications

References 50 publications

Mouse DESC1 Is Located within a Cluster of Seven DESC1-like Genes and Encodes a Type II Transmembrane Serine Protease That Forms Serpin Inhibitory Complexes

Mouse DESC1 Is Located within a Cluster of Seven DESC1-like Genes and Encodes a Type II Transmembrane Serine Protease That Forms Serpin Inhibitory Complexes

Cellular Localization of Membrane-type Serine Protease 1 and Identification of Protease-activated Receptor-2 and Single-chain Urokinase-type Plasminogen Activator as Substrates

Differential expression of a novel serine protease homologue in squamous cell carcinoma of the head and neck

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