Proteolytic activity of prostate-specific antigen (PSA) towards protein substrates and effect of peptides stimulating PSA activity
| Autor: | Johan Malm, Can Hekim, Magnus P. Jonsson, Johanna M. Mattsson, Hannu Koistinen, Suvi Ravela, Ulf-Håkan Stenman, Ale Närvänen |
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| Přispěvatelé: | Clinicum, Department of Clinical Chemistry and Hematology, Haartman Institute (-2014) |
| Rok vydání: | 2014 |
| Předmět: |
Male
MATRIX METALLOPROTEINASES Galectin 3 lcsh:Medicine Peptide urologic and male genital diseases Biochemistry Prostate cancer 0302 clinical medicine Prostate CANCER CELL INVASION BINDING Basic Cancer Research Medicine and Health Sciences HUMAN SEMINAL FLUID Enzyme Inhibitors lcsh:Science chemistry.chemical_classification Tube formation 0303 health sciences Multidisciplinary Membrane Glycoproteins biology Prostate Cancer Prostate Diseases Proteases Trypsin Enzymes Prostate-specific antigen medicine.anatomical_structure Oncology HUMAN-SEMEN 030220 oncology & carcinogenesis Biological Cultures medicine.drug Research Article Urology education Neovascularization Physiologic Research and Analysis Methods Protein Chemistry HUMAN TISSUE KALLIKREINS 03 medical and health sciences medicine Human Umbilical Vein Endothelial Cells Humans Protease Inhibitors Synthetic Peptides 030304 developmental biology Serine protease Enzyme Kinetics lcsh:R Biology and Life Sciences Proteins Cancers and Neoplasms Prostate-Specific Antigen Cell Cultures medicine.disease ANTIANGIOGENIC ACTIVITY Fibronectins Serine Protease Inhibitors SERINE-PROTEASE Kinetics Genitourinary Tract Tumors Insulin-Like Growth Factor Binding Protein 3 chemistry EMERGING ROLES Proteolysis biology.protein Enzymology lcsh:Q 3111 Biomedicine MONOCLONAL-ANTIBODIES Medicinal Chemistry Serine Proteases Peptides |
| Zdroj: | PLoS ONE PLoS ONE; 9(9), no e107819 (2014) PLoS ONE, Vol 9, Iss 9, p e107819 (2014) |
| ISSN: | 1932-6203 |
| Popis: | Prostate-specific antigen (PSA or kallikrein-related peptidase-3, KLK3) exerts chymotrypsin-like proteolytic activity. The main biological function of PSA is the liquefaction of the clot formed after ejaculation by cleavage of semenogelins I and II in seminal fluid. PSA also cleaves several other substrates, which may explain its putative functions in prostate cancer and its antiangiogenic activity. We compared the proteolytic efficiency of PSA towards several protein and peptide substrates and studied the effect of peptides stimulating the activity of PSA with these substrates. An endothelial cell tube formation model was used to analyze the effect of PSA-degraded protein fragments on angiogenesis. We showed that PSA degrades semenogelins I and II much more efficiently than other previously identified protein substrates, e.g., fibronectin, galectin-3 and IGFBP-3. We identified nidogen-1 as a new substrate for PSA. Peptides B2 and C4 that stimulate the activity of PSA towards small peptide substrates also enhanced the proteolytic activity of PSA towards protein substrates. Nidogen-1, galectin-3 or their fragments produced by PSA did not have any effect on endothelial cell tube formation. Although PSA cleaves several other protein substrates, in addition to semenogelins, the physiological importance of this activity remains speculative. The PSA levels in prostate are very high, but several other highly active proteases, such as hK2 and trypsin, are also expressed in the prostate and may cleave protein substrates that are weakly cleaved by PSA. |
| Databáze: | OpenAIRE |
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