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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Wissenschaftlicher Beirat: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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1437-4315
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Band 392, Heft 3

Hefte

Outside or inside: role of the subcellular localization of DP4-like enzymes for substrate conversion and inhibitor effects

Ute Bank / Anke Heimburg / Astrid Wohlfarth / Gudrun Koch / Karsten Nordhoff / Heiko Julius / Martin Helmuth / Doreen Breyer / Dirk Reinhold
  • Institute of Molecular and Clinical Immunology, Otto von Guericke University Magdeburg, D-39120 Magdeburg, Germany
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/ Michael Täger / Siegfried Ansorge
Online erschienen: 18.06.2011 | DOI: https://doi.org/10.1515/bc.2011.025

Abstract

The discovery of the DP4-related enzymes DP8 and DP9 raised controversial discussion regarding the physiological and pathophysiological function of distinct members of the DP4 family. Particularly with regard to their potential relevance in regulating immune functions, it is of interest to know which role the subcellular distribution of the enzymes play. Synthetic substrates as well as low molecular weight inhibitors are widely used as tools, but little is yet known regarding their features in cell experiments, such as their plasma membrane penetration capacity. The fluorogenic substrates Gly-Pro-AMC or (Ala-Pro)2-R110 predominantly detect plasma membrane-bound activities of viable cells (less than 0.1% of fluorochromes R110 or AMC inside viable cells after 1 h incubation). Additionally, the selective and non-selective DP8/9 inhibitors allo-Ile-isoindoline and Lys[Z(NO2)]-pyrrolidide were found to be incapable of passing the plasma membrane easily. This suggests that previously reported cellular effects are not due to inhibition of the cytosolic enzymes DP8 or DP9. Moreover, our enzymatic studies with viable cells provided evidence that DP8 and/or DP9 are also present on the surface of immune cells under certain circumstances and could gain relevance particularly in the absence of DP4 expression. In summary, in cells which do express DP4 on the surface, this archetypical member of the DP4 family is the most relevant peptidase in the regulation of cellular functions.

Keywords: CD26; dipeptidyl peptidase; inhibitors; lymphocytes; neuropeptide Y (NPY); substrates

Artikelinformationen

Corresponding author


Erhalten: 05.07.2010

Angenommen: 01.12.2010

Online erschienen: 18.06.2011

Erschienen im Druck: 01.03.2011


Quellenangabe: Biological Chemistry, Band 392, Heft 3, Seiten 169–187, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/bc.2011.025.

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