Mouse Chromosome 17A3.3 Contains 13 Genes That Encode Functional Tryptic-like Serine Proteases with Distinct Tissue and Cell Expression Patterns

Wong, G. William; Yasuda, Shinsuke; Morokawa, Nasa; Li, Lixin; Stevens, Richard L

doi:10.1074/jbc.m308209200

Cited by 63 publications

(83 citation statements)

References 47 publications

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“…Thus, the first domain shows the highest percentage of identity with ␥1-tryptase (42%) (20), pancreasin (42%) (21), different members of the type II transmembrane serine proteinase family such as matriptase (40%) and matriptase-2 (40%) (22)(23)(24), and the three serine protease domains of polyserase-1 (41%) (10). The second domain is most closely related to matriptase-2 (33% identities), prostasin (30%) (25), ⑀-tryptases (29%) (26), and the three serine protease domains of polyserase-1 (29%) (10).…”

Section: Figmentioning

confidence: 99%

Human Polyserase-2, a Novel Enzyme with Three Tandem Serine Protease Domains in a Single Polypeptide Chain

Cal

Quesada

Llamazares

et al. 2005

Journal of Biological Chemistry

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We have cloned a human cDNA encoding a new serine protease that has been called polyserase-2 (polyserine protease-2) because it is the second identified human enzyme with several tandem serine protease domains in its amino acid sequence. The first serine protease domain contains all characteristic features of these enzymes, whereas the second and third domains lack one residue of the catalytic triad of serine proteases and are predicted to be catalytically inactive. This complex domain organization is also present in the sequences of mouse and rat polyserase-2 and resembles that of polyserase-1, which also contains three serine protease domains in its amino acid sequence. However, polyserase-2 lacks additional domains present in polyserase-1, including a type II transmembrane motif and a low-density lipoprotein receptor A module. Enzymatic analysis demonstrated that both full-length polyserase-2 and its first serine protease domain hydrolyzed synthetic peptides used for assaying serine proteases. Nevertheless, the activity of the isolated domain was greater than that of the entire protein, suggesting that the two catalytically inactive serine protease domains of polyserase-2 may modulate the activity of the first domain. Northern blot analysis showed that polyserase-2 is expressed in fetal kidney; adult skeletal muscle, liver, placenta, prostate, and heart; and tumor cell lines derived from lung and colon adenocarcinomas. Finally, analysis of posttranslational processing mechanisms of polyserase-2 revealed that, contrary to those affecting to the membrane-bound polyserase-1, this novel polyprotein is a secreted enzyme whose three protease domains remain as an integral part of a single polypeptide chain.

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Section: Figmentioning

confidence: 99%

Human Polyserase-2, a Novel Enzyme with Three Tandem Serine Protease Domains in a Single Polypeptide Chain

Cal

Quesada

Llamazares

et al. 2005

Journal of Biological Chemistry

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“…Prss31 is expressed early in developing MCs (42), and the intestine has the highest level of Prss31 mRNA in the body (4). We therefore evaluated the susceptibility of our Prss31-null B6 mice to DSS-induced colitis.…”

Section: Discussionmentioning

confidence: 99%

Importance of Mast Cell Prss31/Transmembrane Tryptase/Tryptase-γ in Lung Function and Experimental Chronic Obstructive Pulmonary Disease and Colitis

Hansbro

Hamilton

Fricker

et al. 2014

Journal of Biological Chemistry

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116

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“…This region has been difficult to sequence because of its high rate of mutation and recombination (21). A comparison of the mouse and human tryptase loci revealed that a chromosomal break and inversion event occurred downstream of the Prss27 gene after mice and humans diverged in evolution (16). Thus, it is likely that this recombination event contributes to the instability of the tryptase locus in humans.…”

Section: Mc-restricted Granule Proteases and Proteoglycansmentioning

confidence: 99%

Mast Cell-restricted Tryptases: Structure and Function in Inflammation and Pathogen Defense

McNeil

Adachi

Stevens

2007

Journal of Biological Chemistry

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Mast cells (MCs) are highly specialized immune cells present in mammals and in lower organisms that predate the development of adaptive immunity. The strong evolutionary pressure to retain MCs for >500 million years suggests critical roles for these cells in our survival. In support of this conclusion, no human has been identified to date that lacks MCs, despite the adverse roles of MCs in systemic anaphylaxis and varied inflammatory disorders. MCs express numerous lineage-restricted neutral proteases, and four members of the chromosome 17A3.3 family of tryptases are preferentially expressed in mouse MCs. The anatomical location of MCs at host-environment interfaces has raised the possibility that some of these enzymes are evolutionally conserved because they are needed for combating infectious organisms. Here we review recent insights into the structure and function of MC tryptases in inflammation and host defense against bacteria and other infectious organisms. MC-restricted Granule Proteases and ProteoglycansA characteristic morphologic feature of mammalian mast cells (MCs) 3 is their electron-dense secretory granules, which contain serglycin proteoglycans (1, 2) bearing heparin (for review see Ref. 3) and chondroitin sulfates diB and E (4, 5). Heparin is the most negatively charged molecule in the body, and each rat and mouse peritoneal MC contains ϳ25 pg of this glycosaminoglycan, thereby explaining the avidity of MCs for cationic dyes (6). The repeating Ser-Gly sequence in serglycin where its glycosaminoglycans are attached cannot be cleaved by any known protease. This protease resistance feature is biologically relevant because the primary function of serglycin proteoglycans in MCs is to provide a scaffold for formation of macromolecular complexes with the cell's varied granule proteases. When properly folded, a positively charged face forms on the surface of each granule protease that allows it to bind tightly to the proteoglycan's negatively charged glycosaminoglycans (7-9).The proteases packaged in the secretory granules of mouse MCs include carboxypeptidase A3 (CPA3), granzyme B, cathepsin G, neuropsin, transmembrane tryptase/tryptase ␥/protease serine member S (Prss) 31, mouse MC protease (mMCP) 1-10, and mMCP-11/Prss34. Definitive evidence of the importance of heparin-containing serglycin proteoglycans in the packaging of specific cassettes of proteases in the MC's granules came with the characterization of N-deacetylase/Nsulfotransferase-2 (NDST-2)-null mice (10, 11). NDST-2 is essential for heparin biosynthesis and is preferentially expressed in MCs. Because of the loss of fully sulfated heparin, the MCs in the skin and peritoneal cavities of NDST-2-null mice store reduced amounts of mMCP-6 and almost no CPA3, mMCP-4, and mMCP-5, even though all four MC-restricted protease genes are transcribed at normal rates. The accumulated data led to the current view that serglycin proteoglycans are essential for the post-translational processing and granule accumulation of most, if not all, proteases stor...

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Mouse Chromosome 17A3.3 Contains 13 Genes That Encode Functional Tryptic-like Serine Proteases with Distinct Tissue and Cell Expression Patterns

Cited by 63 publications

References 47 publications

Human Polyserase-2, a Novel Enzyme with Three Tandem Serine Protease Domains in a Single Polypeptide Chain

Human Polyserase-2, a Novel Enzyme with Three Tandem Serine Protease Domains in a Single Polypeptide Chain

Importance of Mast Cell Prss31/Transmembrane Tryptase/Tryptase-γ in Lung Function and Experimental Chronic Obstructive Pulmonary Disease and Colitis

Mast Cell-restricted Tryptases: Structure and Function in Inflammation and Pathogen Defense

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