Substrates of the prostate-specific serine protease prostase/KLK4 defined by positional-scanning peptide libraries

The Prostate
M MatsumuraP S Nelson

Abstract

Prostase/KLK4 is a member of the human kallikrein (KLK) gene family that is expressed in prostate epithelial cells under the regulation of androgenic hormones. In this study, we sought to characterize the substrate specificity of KLK4 in order to gain insight into potential physiological roles of the enzyme. A chimeric form of KLK4 was constructed in which the pro-region of KLK4 was replaced with the signal and propeptide sequence of trypsinogen (proT-KLK4) to create an activation site susceptible to enterokinase cleavage. proT-KLK4 was expressed in Drosophila S2 cells, purified, and activated with enterokinase to generate mature KLK4. The extended substrate specificity of KLK4 was defined by screening tetrapeptide positional scanning synthetic combinatorial libraries (PS-SCL). The preferred P1-P4 positions as determined by PS-SCL were: P1-Arg; P2-Gln/Leu/Val; P3-Gln/Ser/Val; P4-Ile/Val. The trypsin-like specificity of KLK4 was further confirmed using synthetic chromogenic peptides. Based upon the optimal cleavage site residues, a database search for potential KLK4 substrates identified several proteins with potential roles mediating normal prostate physiology or neoplastic growth including KLK3/PSA, parathyroid hormone-related...Continue Reading

References

Oct 29, 1991·Biochemistry·E W DavieW Kisiel
Sep 15, 1989·Clinica Chimica Acta; International Journal of Clinical Chemistry·M KimlandA Borgström
Sep 1, 1988·The New England Journal of Medicine·A E BroadusA F Stewart
Aug 2, 1994·Proceedings of the National Academy of Sciences of the United States of America·Y KitamotoJ E Sadler
May 29, 1997·International Journal of Cancer. Journal International Du Cancer·G FrenetteJ Y Dube
Feb 18, 1998·Journal of Dental Research·J P SimmerJ D Bartlett
Jun 24, 1998·Journal of the National Cancer Institute·A WolkD Trichopoulos
Oct 6, 1998·Critical Reviews in Clinical Laboratory Sciences·H G RittenhouseA W Partin
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·P S NelsonK Wang
Jun 28, 2000·Proceedings of the National Academy of Sciences of the United States of America·J L HarrisC S Craik
Sep 21, 2000·Journal of the National Cancer Institute·H Yu, T Rohan
Oct 18, 2000·Endocrinology and Metabolism Clinics of North America·G J Strewler
Apr 27, 2001·Seminars in Cancer Biology·W G Stetler-Stevenson, A E Yu
Jun 18, 2002·Clinical & Experimental Metastasis·Mario Del RossoVincenzo Chiarugi

❮ Previous
Next ❯

Citations

Aug 10, 2006·Breast Cancer Research and Treatment·Miltiadis Paliouras, Eleftherios P Diamandis
Jul 7, 2009·The Journal of Biological Chemistry·James P SimmerJan C-C Hu
Jun 26, 2007·Cells, Tissues, Organs·Mitchell G LawrenceJudith A Clements
Jun 28, 2006·Biological Chemistry·Miltiadis Paliouras, Eleftherios P Diamandis
Jun 28, 2006·Biological Chemistry·Nathalie Heuzé-Vourc'hYves Courty
Jun 28, 2006·Biological Chemistry·Chistina V ObiezuEleftherios P Diamandis
Mar 30, 2007·Biological Chemistry·Nader MemariLiu-Ying Luo
Nov 3, 2007·Biological Chemistry·Carla A BorgoñoEleftherios P Diamandis
Jul 17, 2008·Biological Chemistry·Yuhe LuJames P Simmer
Feb 12, 2010·Future Oncology·Konstantinos Mavridis, Andreas Scorilas
Sep 18, 2013·Clinical & Experimental Metastasis·Ying DongJudith A Clements
Sep 27, 2015·Biochimie·Magdalena KalinskaJan Potempa
Oct 1, 2015·Molecular Biology and Evolution·Patrícia Isabel MarquesSusana Seixas
Apr 23, 2011·International Journal of Pharmaceutics·Meredith R ClarkPatrick F Kiser
Feb 26, 2010·Biological Chemistry·Joakim E SwedbergJonathan M Harris
Apr 25, 2008·Bioorganic & Medicinal Chemistry·Mark D Lim, Charles S Craik
Dec 13, 2006·Current Opinion in Chemical Biology·Scott L Diamond
Sep 5, 2006·Journal of Molecular Biology·Mekdes DebelaPeter Goettig
Feb 28, 2014·Expert Opinion on Therapeutic Targets·Konstantinos MavridisAndreas Scorilas
Jul 10, 2010·Biochimie·Peter GoettigHans Brandstetter
Jul 30, 2014·Frontiers in Physiology·John D Bartlett, James P Simmer
Feb 18, 2016·Critical Reviews in Clinical Laboratory Sciences·Panagiota S FilippouEleftherios P Diamandis
Jul 3, 2016·Molecular & Cellular Proteomics : MCP·Theano D KarakostaAndrei P Drabovich
Oct 14, 2017·Expert Review of Proteomics·Lakmali Munasinghage Silva, Judith Ann Clements
Jul 6, 2018·Biological Chemistry·Shihui GuoPeter Goettig
Jun 3, 2006·The Journal of Biological Chemistry·Mekdes DebelaPeter Goettig
Feb 24, 2015·Nature Reviews. Drug Discovery·Ioannis PrassasEleftherios P Diamandis
May 18, 2019·ELife·Sawan Kumar JhaMichael Jeltsch

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.