Outside or inside: role of the subcellular localization of DP4-like enzymes for substrate conversion and inhibitor effects
-
Ute Bank
,
Anke Heimburg
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.
©2011 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Guest Editorial
- Highlight: Dipeptidyl peptidase 4 and related proteins
- HIGHLIGHT: DIPEPTIDYL PEPTIDASE 4 AND RELATED PROTEINS
- Novel aspects of cellular action of dipeptidyl peptidase IV/CD26
- Outside or inside: role of the subcellular localization of DP4-like enzymes for substrate conversion and inhibitor effects
- Expression and spatial heterogeneity of dipeptidyl peptidases in endothelial cells of conduct vessels and capillaries
- Expression and role of the cell surface protease seprase/fibroblast activation protein-α (FAP-α) in astroglial tumors
- DPP-4 inhibition increases GIP and decreases GLP-1 incretin effects during intravenous glucose tolerance test in Wistar rats
- Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers
- Selective inhibition of dipeptidyl peptidase 4 by targeting a substrate-specific secondary binding site
- PETIR-001, a dual inhibitor of dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN), ameliorates experimental autoimmune encephalomyelitis in SJL/J mice
- CELL BIOLOGY AND SIGNALING
- Identification and characterisation of novel Mss4-binding Rab GTPases
- Identification of lily pollen 14-3-3 isoforms and their subcellular and time-dependent expression profile
- PROTEOLYSIS
- Myeloperoxidase-catalyzed oxidative inactivation of human kininogens: the impairment of kinin-precursor and prekallikrein-binding functions
Articles in the same Issue
- Guest Editorial
- Highlight: Dipeptidyl peptidase 4 and related proteins
- HIGHLIGHT: DIPEPTIDYL PEPTIDASE 4 AND RELATED PROTEINS
- Novel aspects of cellular action of dipeptidyl peptidase IV/CD26
- Outside or inside: role of the subcellular localization of DP4-like enzymes for substrate conversion and inhibitor effects
- Expression and spatial heterogeneity of dipeptidyl peptidases in endothelial cells of conduct vessels and capillaries
- Expression and role of the cell surface protease seprase/fibroblast activation protein-α (FAP-α) in astroglial tumors
- DPP-4 inhibition increases GIP and decreases GLP-1 incretin effects during intravenous glucose tolerance test in Wistar rats
- Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers
- Selective inhibition of dipeptidyl peptidase 4 by targeting a substrate-specific secondary binding site
- PETIR-001, a dual inhibitor of dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN), ameliorates experimental autoimmune encephalomyelitis in SJL/J mice
- CELL BIOLOGY AND SIGNALING
- Identification and characterisation of novel Mss4-binding Rab GTPases
- Identification of lily pollen 14-3-3 isoforms and their subcellular and time-dependent expression profile
- PROTEOLYSIS
- Myeloperoxidase-catalyzed oxidative inactivation of human kininogens: the impairment of kinin-precursor and prekallikrein-binding functions
