Molecular characterization of a novel dipeptidyl peptidase like 2-short form (DPL2-s) that is highly expressed in the brain and lacks dipeptidyl peptidase activity

Chen, Tong; Ajami, Katerina; McCaughan, Geoffrey W.; Gai, Wei; Gorrell, Mark D.; Abbott, Catherine A.

doi:10.1016/j.bbapap.2005.09.013

Cited by 23 publications

(24 citation statements)

References 30 publications

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“…While DPL1 is expressed exclusively in the brain as two variants, i.e. a short and a long form, DPL2 is found in brain, pancreas and adrenal gland [5,62]. The long form DPL1-L is an 859 amino acid protein with a molecular weight of 97 kDa, whereas the short form, DPL1-S, consists of 803 amino acids with a reported molecular weight of 91 kDa [4,6].…”

Section: Dpp4 Gene Familymentioning

confidence: 99%

“…DPP-like protein 1 (DPL1) and DPP-like protein 2 (DPL2) lack DPP4-like activity because of mutations at their active sites. Both of them are type II membranebound glycoproteins, suggested to interact with the voltage-gated potassium channel Kv4 [4][5][6][61][62][63]. While DPL1 is expressed exclusively in the brain as two variants, i.e.…”

Section: Dpp4 Gene Familymentioning

confidence: 99%

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Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

Wagner¹,

Klemann²,

Stephan

et al. 2016

Clinical and Experimental Immunology

100

107

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SummaryDipeptidyl peptidase (DPP) 4 (CD26, DPP4) is a multi-functional protein involved in T cell activation by co-stimulation via its association with adenosine deaminase (ADA), caveolin-1, CARMA-1, CD45, mannose-6-phosphate/insulin growth factor-II receptor (M6P/IGFII-R) and C-X-C motif receptor 4 (CXC-R4). The proline-specific dipeptidyl peptidase also modulates the bioactivity of several chemokines. However, a number of enzymes displaying either DPP4-like activities or representing structural homologues have been discovered in the past two decades and are referred to as DPP4 activity and/or structure homologue (DASH) proteins. Apart from DPP4, DASH proteins include fibroblast activation protein alpha (FAP), DPP8, DPP9, DPP4-like protein 1 (DPL1, DPP6, DPPX L, DPPX S), DPP4-like protein 2 (DPL2, DPP10) from the DPP4-gene family S9b and structurally unrelated enzyme DPP2, displaying DPP4-like activity. In contrast, DPP6 and DPP10 lack enzymatic DPP4-like activity. These DASH proteins play important roles in the immune system involving quiescence (DPP2), proliferation (DPP8/DPP9), antigen-presenting (DPP9), costimulation (DPP4), T cell activation (DPP4), signal transduction (DPP4, DPP8 and DPP9), differentiation (DPP4, DPP8) and tissue remodelling (DPP4, FAP). Thus, they are involved in many pathophysiological processes and have therefore been proposed for potential biomarkers or even drug targets in various cancers (DPP4 and FAP) and inflammatory diseases (DPP4, DPP8/DPP9). However, they also pose the challenge of drug selectivity concerning other DASH members for better efficacy and/or avoidance of unwanted side effects. Therefore, this review unravels the complex roles of DASH proteins in immunology.Keywords: antigen presentation/processing, CD26, co-stimulation, DPP4 activity and/or structure homologue proteins (DASH), signal transductionThe dipeptidyl peptidase (DPP)4 family of DPP4 activity and/or structure homologue (DASH) proteins Within the last two decades a number of enzymes have been discovered to also display DPP4-like activity or are structural homologues to DPP4. These enzymes/proteins are referred to as DPP4 activity and/or structure homologue (DASH) proteins, and can be grouped into the DPP4 gene family and non-related DPP4-like enzymes. Except for DPL1 and DPL2, all members display DPP4-like activity with neutral to basic pH optima and similar inhibition profiles [6,7]. DPP4 (CD26). DPP4 (CD26) is the best-known DASH protein and has been described in detail elsewhere [7][8][9].

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Section: Dpp4 Gene Familymentioning

confidence: 99%

Section: Dpp4 Gene Familymentioning

confidence: 99%

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

Wagner¹,

Klemann²,

Stephan

et al. 2016

Clinical and Experimental Immunology

100

107

View full text Add to dashboard Cite

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“…As far as DPP10 is concerned, the protein was shown to be glycosylated [4]. However, those findings were obtained with the de-glycosylating enzyme PNGase F under conditions unsuitable for analysis in living cells as investigated in our study.…”

Section: Discussionmentioning

confidence: 58%

“…In consideration of previous data reporting that DPP10 is not expressed in the mammalian heart [1,4,24], we decided to solve this issue by checking if DPP10 is expressed in the human heart through the sensitive RT-PCR technique. We designed a set of primers specific for DPP10 and performed RT-PCR on RNAs from either human heart biopsies or human brain used as positive control.…”

Section: Tunicamycin Treatment Affects Native I To Currents In Human mentioning

confidence: 99%

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Impaired glycosylation blocks DPP10 cell surface expression and alters the electrophysiology of I to channel complex

Cotella

Radicke

Bortoluzzi

et al. 2010

Pflugers Arch - Eur J Physiol

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DPP10 is a transmembrane glycosylated protein belonging to the family of dipeptidyl aminopeptidase-like proteins (DPPLs). DPPLs are auxiliary subunits involved in the regulation of voltage-gated Kv4 channels, key determinants of cardiac and neuronal excitability. Although it is known that DPPLs are needed to generate native-like currents in heterologous expression systems, the molecular basis of this involvement are still poorly defined. In this study, we investigated the functional relevance of DPP10 glycosylation in modulating Kv4.3 channel activities. Using transfected Chinese hamster ovary (CHO) cells to reconstitute Kv4 complex, we show that the pharmacological inhibition of DPP10 glycosylation by tunicamycin and neuraminidase affects transient outward potassium current (I (to)) kinetics. Tunicamycin completely blocked DPP10 glycosylation and reduced DPP10 cell surface expression. The accelerating effects of DPP10 on Kv4.3 current kinetics, i.e. on inactivation and recovery from inactivation, were abolished. Neuraminidase produced different effects on current kinetics than tunicamycin, i.e., shifted the voltage dependence to more negative potentials. The effects of tunicamycin on the native I (to) currents of human atrial myocytes expressing DPP10 were similar to those of the KV4.3/KChIP2/DPP10 complex in CHO cells. Our results suggest that N-linked glycosylation of DPP10 plays an important role in modulating Kv4 channel activities.

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Proteases in the Nervous System

Cynis

Lichtenthaler

Wagner

et al. 2013

Proteases: Structure and Function

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Molecular characterization of a novel dipeptidyl peptidase like 2-short form (DPL2-s) that is highly expressed in the brain and lacks dipeptidyl peptidase activity

Cited by 23 publications

References 30 publications

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

Impaired glycosylation blocks DPP10 cell surface expression and alters the electrophysiology of I to channel complex

Proteases in the Nervous System

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