| Promiscuous processing of human alphabeta-protryptases by cathepsins L, B, and C. | |
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MedLine Citation:
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PMID: 21562164 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human α- and β-protryptase zymogens are abundantly and selectively produced by mast cells, but the mechanism(s) by which they are processed is uncertain. β-Protryptase is sequentially processed in vitro by autocatalysis at R(-3) followed by cathepsin (CTS) C proteolysis to the mature enzyme. However, mast cells from CTSC-deficient mice successfully convert protryptase (pro-murine mast cell protease-6) to mature murine mast cell protease-6. α-Protryptase processing cannot occur by trypsin-like enzymes due to an R(-3)Q substitution. Thus, biological mechanisms for processing these zymogens are uncertain. β-Tryptase processing activity(ies) distinct from CTSC were partially purified from human HMC-1 cells and identified by mass spectroscopy to include CTSB and CTSL. Importantly, CTSB and CTSL also directly process α-protryptase (Q(-3)) and mutated β-protryptase (R(-3)Q) as well as wild-type β-protryptase to maturity, indicating no need for autocatalysis, unlike the CTSC pathway. Heparin promoted tryptase tetramer formation and protected tryptase from degradation by CTSB and CTSL. Thus, CTSL and CTSB are capable of directly processing both α- and β-protryptases from human mast cells to their mature enzymatically active products. |
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Authors:
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Quang T Le; Hae-Ki Min; Han-Zhang Xia; Yoshihiro Fukuoka; Nobuhiko Katunuma; Lawrence B Schwartz |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-05-11 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 186 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-06-07 Completed Date: 2011-10-07 Revised Date: 2012-10-09 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 7136-43 Citation Subset: AIM; IM |
Affiliation:
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Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cathepsin B
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metabolism Cathepsin C / metabolism Cathepsin L / metabolism Cathepsins / analysis, metabolism* Cell Line Enzyme Precursors / metabolism* Heparin / pharmacology Humans Mass Spectrometry Mast Cells / enzymology*, metabolism Protein Processing, Post-Translational* Tryptases / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI027517-19/AI/NIAID NIH HHS; R01-AI27517/AI/NIAID NIH HHS; U19 AI077435-02S1/AI/NIAID NIH HHS; U19-AI77435/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Precursors; 9005-49-6/Heparin; EC 3.4.-/Cathepsins; EC 3.4.14.1/Cathepsin C; EC 3.4.21.59/Tpsab1 protein, mouse; EC 3.4.21.59/Tryptases; EC 3.4.22.1/Cathepsin B; EC 3.4.22.15/Cathepsin L |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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