Please use this identifier to cite or link to this item: http://hdl.handle.net/11434/407
Title: Identification of novel dipeptidyl peptidase 9 substrates by two-dimensional differential in-gel electrophoresis.
Epworth Authors: Stephens, Andrew
Other Authors: Zhang, Hui
Maqsudi, Sadiqa
Rainczuk, Adam
Duffield, Nadine
Lawrence, Josie
Keane, Fiona
Justa-Schuch, Daniela
Geiss-Friedlander, Ruth
Gorrell, Mark
Keywords: Epworth Research Institute, Epworth HealthCare, Richmond, Victoria, Australia
Dipeptidyl Peptidase 9, Mouse
Dipeptidyl Peptidase 9, Human
Function
Mass Spectrometry
Spectrometry, Mass
Spectrum Analysis, Mass
Analysis, Mass Spectrum
Chromogenic Substrates
Antigens
Serine Proteases
Epidermal Growth Factor
Electrophoresis
Fibroblasts
Proteolysis
Protein Digestion
Protein Degradation
DIGE
Issue Date: Jul-2015
Publisher: Wiley
Citation: The FEBS Journal 2015 Jul 14
Abstract: Dipeptidyl peptidase 9 (DPP9) is a member of the S9B/DPPIV (DPP4) serine protease family, which cleaves N-terminal dipeptides at an Xaa-Pro consensus motif. Cytoplasmic DPP9 has roles in epidermal growth factor signalling and in antigen processing, whilst the role of the recently discovered nuclear form of DPP9 is unknown. Mice lacking DPP9 proteolytic activity die as neonates. We applied a modified 2D differential in-gel electrophoresis approach to identify novel DPP9 substrates, using mouse embryonic fibroblasts lacking endogenous DPP9 activity. A total of 111 potential new DPP9 substrates were identified, with nine proteins/peptides confirmed as DPP9 substrates by MALDI-TOF or immunoblotting. Moreover, we also identified the dipeptide Val-Ala as a consensus site for DPP9 cleavage that was not recognized by DPP8, suggesting different in vivo roles for these closely related enzymes. The relative kinetics for the cleavage of these nine candidate substrates by DPP9, DPP8 and DPP4 were determined. This is the first identification of DPP9 substrates from cells lacking endogenous DPP9 activity. These data greatly expand the potential roles of DPP9 and suggest different in vivo roles for DPP9 and DPP8.
URI: http://hdl.handle.net/11434/407
DOI: 10.1111/febs.13371
PubMed URL: http://www.ncbi.nlm.nih.gov/pubmed/26175140
ISSN: 1742-4658
Journal Title: The FEBS Journal © Federation of European Biochemical Societies
Type: Journal Article
Affiliated Organisations: Molecular Hepatology, Liver Injury and Cancer Group, Centenary Institute, Sydney Medical School, University of Sydney, Australia
Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia
Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia
Department of Molecular Biology, Faculty of Medicine, Georg-August-University of Goettingen, Germany
Type of Clinical Study or Trial: Descriptive Study
Appears in Collections:Pre-Clinical

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