The Activity of a Type II Transmembrane Serine Protease, Matriptase, Is Dependent Solely on the Catalytic Domain

2009 ◽  
Vol 73 (2) ◽  
pp. 454-456 ◽  
Author(s):  
Kenji KOJIMA ◽  
Satoshi TSUZUKI ◽  
Tohru FUSHIKI ◽  
Kuniyo INOUYE
Keyword(s):  
Serine Protease ◽  
Catalytic Domain ◽  
Type Ii ◽  
Transmembrane Serine Protease

Identification of the first synthetic inhibitors of the type II transmembrane serine protease TMPRSS2 suitable for inhibition of influenza virus activation

2013 ◽  
Vol 452 (2) ◽  
pp. 331-343 ◽  
Author(s):  
Daniela Meyer ◽  
Frank Sielaff ◽  
Maya Hammami ◽  
Eva Böttcher-Friebertshäuser ◽  
Wolfgang Garten ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Serine Protease ◽  
Catalytic Domain ◽  
Serine Proteinase ◽  
Airway Epithelial Cells ◽  
Influenza Viruses ◽  
Surface Glycoprotein ◽  
Type Ii ◽  
Virus Propagation ◽  
Transmembrane Serine Protease

TMPRSS2 (transmembrane serine proteinase 2) is a multidomain type II transmembrane serine protease that cleaves the surface glycoprotein HA (haemagglutinin) of influenza viruses with a monobasic cleavage site, which is a prerequisite for virus fusion and propagation. Furthermore, it activates the fusion protein F of the human metapneumovirus and the spike protein S of the SARS-CoV (severe acute respiratory syndrome coronavirus). Increased TMPRSS2 expression was also described in several tumour entities. Therefore TMPRSS2 emerged as a potential target for drug design. The catalytic domain of TMPRSS2 was expressed in Escherichia coli and used for an inhibitor screen with previously synthesized inhibitors of various trypsin-like serine proteases. Two inhibitor types were identified which inhibit TMPRSS2 in the nanomolar range. The first series comprises substrate analogue inhibitors containing a 4-amidinobenzylamide moiety at the P1 position, whereby some of these analogues possess inhibition constants of approximately 20 nM. An improved potency was found for a second type derived from sulfonylated 3-amindinophenylalanylamide derivatives. The most potent derivative of this series inhibits TMPRSS2 with a Ki value of 0.9 nM and showed an efficient blockage of influenza virus propagation in human airway epithelial cells. On the basis of the inhibitor studies, a series of new fluorogenic substrates containing a D-arginine residue at the P3 position was synthesized, some of them were efficiently cleaved by TMPRSS2.

scholarly journals Phenotypic Analysis of Mice Lacking the Tmprss2-Encoded Protease

2006 ◽  
Vol 26 (3) ◽  
pp. 965-975 ◽  
Author(s):  
Tom S. Kim ◽  
Cynthia Heinlein ◽  
Robert C. Hackman ◽  
Peter S. Nelson
Keyword(s):  
Serine Protease ◽  
Serine Proteases ◽  
Biological Activities ◽  
Type Ii ◽  
Phenotypic Analysis ◽  
Normal Prostate ◽  
Prostate Hyperplasia ◽  
Transmembrane Serine Protease

ABSTRACT Tmprss2 encodes an androgen-regulated type II transmembrane serine protease (TTSP) expressed highly in normal prostate epithelium and has been implicated in prostate carcinogenesis. Although in vitro studies suggest protease-activated receptor 2 may be a substrate for TMPRSS2, the in vivo biological activities of TMPRSS2 remain unknown. We generated Tmprss2 −/− mice by disrupting the serine protease domain through homologous recombination. Compared to wild-type littermates, Tmprss2 −/− mice developed normally, survived to adulthood with no differences in protein levels of prostatic secretions, and exhibited no discernible abnormalities in organ histology or function. Loss of TMPRSS2 serine protease activity did not influence fertility, reduce survival, result in prostate hyperplasia or carcinoma, or alter prostatic luminal epithelial cell regrowth following castration and androgen replacement. Lack of an observable phenotype in Tmprss2 −/− mice was not due to transcriptional compensation by closely related Tmprss2 homologs. We conclude that the lack of a discernible phenotype in Tmprss2 −/− mice suggests functional redundancy involving one or more of the type II transmembrane serine protease family members or other serine proteases. Alternatively, TMPRSS2 may contribute a specialized but nonvital function that is apparent only in the context of stress, disease, or other systemic perturbation.

The Type II Transmembrane Serine Protease, Matriptase-2: Possible Links to Cancer?

2010 ◽  
Vol 10 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Andrew Sanders ◽  
Siobhan Webb ◽  
Christian Parr ◽  
Malcolm Mason ◽  
Wen Jiang
Keyword(s):  
Serine Protease ◽  
Type Ii ◽  
Transmembrane Serine Protease

TMPRSS4 is a type II transmembrane serine protease involved in cancer and viral infections

2012 ◽  
Vol 393 (9) ◽  
pp. 907-914 ◽  
Author(s):  
Anke Ohler ◽  
Christoph Becker-Pauly
Keyword(s):  
Serine Protease ◽  
Serine Proteases ◽  
Viral Infections ◽  
Proteolytic Enzymes ◽  
Metastatic Potential ◽  
Influenza Viruses ◽  
Type Ii ◽  
Serine Protease Family ◽  
Transmembrane Serine Protease ◽  
Almost All

Abstract Proteolytic enzymes are involved in almost all biological processes reflecting their importance in health and disease. The human genome contains nearly 600 protease-encoding genes forming more than 2% of the total human proteome. The serine proteases, with about 180 members, built the oldest and second largest family of human proteases. Ten years ago, a novel serine protease family named the type II transmembrane family (TTSP) was identified. This minireview summarizes the up-to-date knowledge about the still growing TTSPs, particularly focusing on the pathophysiological functions of the family member type II transmembrane serine protease (TMPRSS) 4. Recent studies provided important data on TMPRSS4 activity associated with the spreading of influenza viruses, mediated by the cleavage of hemagglutinin. Progression and metastatic potential of several cancers is concordant with an increased expression of TMPRSS4, though being a possible diagnostic marker. However, to benefit from TMPRSS4 as a therapeutic target, more data concerning its physiological relevance are needed, as done by a specific morpholino knockdown in zebrafish embryos.

scholarly journals Interaction of Protein C Inhibitor with the Type II Transmembrane Serine Protease Enteropeptidase

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e39262 ◽  
Author(s):  
Thomas A. Prohaska ◽  
Felix C. Wahlmüller ◽  
Margareta Furtmüller ◽  
Margarethe Geiger
Keyword(s):  
Serine Protease ◽  
Protein C ◽  
Type Ii ◽  
Protein C Inhibitor ◽  
Transmembrane Serine Protease

scholarly journals Autosomal Recessive Ichthyosis with Hypotrichosis Caused by a Mutation in ST14, Encoding Type II Transmembrane Serine Protease Matriptase

2007 ◽  
Vol 80 (3) ◽  
pp. 467-477 ◽  
Author(s):  
Lina Basel-Vanagaite ◽  
Revital Attia ◽  
Akemi Ishida-Yamamoto ◽  
Limor Rainshtein ◽  
Dan Ben Amitai ◽  
...  
Keyword(s):  
Serine Protease ◽  
Autosomal Recessive ◽  
Type Ii ◽  
Transmembrane Serine Protease ◽  
Recessive Ichthyosis

scholarly journals The role of type II transmembrane serine protease-mediated signaling in cancer

FEBS Journal ◽  
2016 ◽  
Vol 284 (10) ◽  
pp. 1421-1436 ◽  
Author(s):  
Lauren M. Tanabe ◽  
Karin List
Keyword(s):  
Serine Protease ◽  
Type Ii ◽  
Transmembrane Serine Protease

Changes in the Distribution of Type II Transmembrane Serine Protease, TMPRSS2 and in Paracellular Permeability in IPEC-J2 Cells Exposed to Oxidative Stress

Inflammation ◽  
2014 ◽  
Vol 38 (2) ◽  
pp. 775-783 ◽  
Author(s):  
Erzsebet Paszti-Gere ◽  
Reka Fanni Barna ◽  
Csaba Kovago ◽  
Ipoly Szauder ◽  
Gabriella Ujhelyi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Serine Protease ◽  
Paracellular Permeability ◽  
Type Ii ◽  
Transmembrane Serine Protease

Synthesis and evaluation of the sunflower derived trypsin inhibitor as a potent inhibitor of the type II transmembrane serine protease, matriptase

2001 ◽  
Vol 11 (18) ◽  
pp. 2515-2519 ◽  
Author(s):  
Ya-Qiu Long ◽  
Sheau-Ling Lee ◽  
Chen-Yong Lin ◽  
Istvan J Enyedy ◽  
Shaomeng Wang ◽  
...  
Keyword(s):  
Serine Protease ◽  
Trypsin Inhibitor ◽  
Potent Inhibitor ◽  
Type Ii ◽  
Transmembrane Serine Protease
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