Document Detail


Differences in the activation mechanism between the alpha and beta subunits of human meprin.
MedLine Citation:
PMID:  12817480     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Meprins are zinc-endopeptidases of the astacin family, which are expressed as membrane-bound or secreted forms in renal and intestinal brush-border membranes of mouse, rat and man. There are two types of meprin subunits, alpha and beta, which form disulfide-bonded homo- and heterodimers; further oligomerization is mediated by non-covalent interactions. Both subunits are translated as proenzymes that have to be activated by removal of an N-terminal propeptide. In the gut, the most probable activator is trypsin. In addition, plasmin has been shown to activate the human alpha subunit in colorectal cancer tissue. In the present study we have overexpressed the human meprin alpha subunit and a His-tagged soluble tail-switch-mutant of meprin beta in Baculovirus-infected insect cells. The recombinant homo-oligomeric proteins were purified by gel filtration and affinity chromatography with yields of up to 10 mg/l cell culture medium and analyzed with regard to their activation mechanism. While both alpha and beta homo-oligomers are activated by trypsin, only meprin alpha homo-oligomers are processed to their mature form by plasmin. These results indicate a different accessibility of the propeptide in meprin homo-oligomers and suggest an explanation for the appearance of meprin hetero-oligomers consisting of active alpha, but latent beta subunits.
Authors:
Christoph Becker; Markus-N Kruse; Kristina A Slotty; Danny Köhler; J Robin Harris; Sandra Rösmann; Erwin E Sterchi; Walter Stöcker
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological chemistry     Volume:  384     ISSN:  1431-6730     ISO Abbreviation:  Biol. Chem.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-06-23     Completed Date:  2004-02-10     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9700112     Medline TA:  Biol Chem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  825-31     Citation Subset:  IM    
Affiliation:
Institut für Zoophysiologie, Molekulare Physiologie, Westfälische Wilhelms-Universität Münster, Hindenburgplatz 55, D-48143 Münster, Germany.
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MeSH Terms
Descriptor/Qualifier:
Chromatography, Gel
Enzyme Activation / drug effects
Enzyme Precursors / metabolism
Fibrinolysin / pharmacology
Humans
Immunoblotting
Metalloendopeptidases / chemistry,  metabolism*
Microscopy, Electron
Protein Subunits / metabolism
Recombinant Proteins / chemistry,  metabolism
Trypsin / pharmacology
Zinc / chemistry,  metabolism*
Chemical
Reg. No./Substance:
0/Enzyme Precursors; 0/Protein Subunits; 0/Recombinant Proteins; 7440-66-6/Zinc; EC 3.4.21.4/Trypsin; EC 3.4.21.7/Fibrinolysin; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.18/meprin A; EC 3.4.24.63/meprin B

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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