Direct Association of Adenosine Deaminase with a T Cell Activation Antigen, CD26

Kameoka, Junichi; Tanaka, Toshiaki; Nojima, Yoshihisa; Schlossman, Stuart F.; Morimoto, Chikao

doi:10.1126/science.8101391

Cited by 490 publications

(351 citation statements)

References 33 publications

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“…The set of KIEs for the three ADAs were determined under competitive conditions. The intrinsic [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] N], [6-13 C], and [6- 30 Adenylate kinase (AK), pyruvate kinase (PK), hexokinase, and bovine spleen adenosine deaminase (BtADA) were purchased from Sigma. Phospho-D-ribosyl-1-pyrophosphate (PRPP) synthase and adenine phosphoribosyltransferase (APRTase) were purified according to the methods reported previously.…”

Section: Introductionmentioning

confidence: 99%

Transition-State Variation in Human, Bovine, and Plasmodium falciparum Adenosine Deaminases

2007

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Adenosine deaminases (ADAs) from human, bovine and Plasmodium falciparum sources were analyzed by kinetic isotope effects (KIEs) and shown to have distinct but related transition states. Human adenosine deaminase (HsADA) is present in most mammalian cells and is involved in Band T-cell development. The ADA from Plasmodium falciparum (PfADA) is essential in this purine auxotroph and its inhibition is expected to have therapeutic effects for malaria. Therefore ADA is of continuing interest for inhibitor design. where N1 protonation is partial and the bond order to the attacking hydroxyl nucleophile is nearly complete. The key structural variation among PfADA, HsADA and BtADA transition states lies in the degree of N1 protonation with the decreased bond lengths of 1.92 Å, 1.55 Å and 1.28 Å, respectively. Thus, PfADA has the earliest and BtADA has most developed transition state. This conclusion is consistent with the 20 to 36-fold increase of k cat in comparing PfADA with HsADA and BtADA.

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Section: Introductionmentioning

confidence: 99%

Transition-State Variation in Human, Bovine, and Plasmodium falciparum Adenosine Deaminases

2007

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“…Since we discovered adenosine deaminase (ADA, EC 3.5.4.4) on the surface of hematopoietic cells [8], ecto-ADA has also been implicated in controling the extracellular concentration of the nucleoside. ADA binds to the cell surface of T lymphocytes through the activation marker CD26 [9], which is also known as dipeptidylpeptidase IV or ADA binding protein.…”

Section: Introductionmentioning

confidence: 99%

Adenosine deaminase affects ligand‐induced signalling by interacting with cell surface adenosine receptors

et al. 1996

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Adenosine deaminase (ADA) is not only a cytosolic enzyme but can be found as an ecto-enzyme. At the plasma membrane, an adenosine deaminase binding protein (CD26, also known as dipeptidylpeptidase IV) has been identified but the functional role of this ADMCD26 complex is unclear. Here by confocal microscopy, affinity chromatography and coprecipitation experiments we show that A 1 adenosine receptor (AIR) is a second ecto-ADA binding protein. Binding of ADA to AtR increased its affinity for the ligand thus suggesting that ADA was needed for an effective coupling between A~R and heterotrimeric G proteins. This was confirmed by the fact that ASA, independently of its catalytic behaviour, enhanced the ligand-induced second messenger production via AtR. These findings demonstrate that, apart from the cleavage of adenosine, a further role of ecto-adenosine deaminase on the cell surface is to facilitate the signal transduction via AIR.

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“…Its extracellular domain encodes a membrane-associated dipeptidyl peptidase IV (DPPIV) activity, able to cleave amino-terminal dipeptides from polypeptides with either L-proline or L-alanine at the penultimate position, including chemokines involved in leukocyte function (Oravecz et al, 1997;Proost et al, 1998). CD26 is also involved in T-cell activation, owing to its association with CD45, mannose 6-phosphate/insulin-like growth factor II receptor and adenosine deaminase (ADA) (Morimoto et al, 1989;Dang et al, 1990aDang et al, -d, 1991Torimoto et al, 1991;Kameoka et al, 1993;Morrison et al, 1993;Ikushima et al, 2000). Additionally, its DPPIV enzyme activity has a key role in various aspects of T-cell activation, as demonstrated by studies using DPPIV inhibitors, soluble CD26/DPPIV molecules or CD26 genetic mutants (Flentke et al, 1991;Tanaka et al, 1993Tanaka et al, , 1994Steinbrecher et al, 2001).…”

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confidence: 99%

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

et al. 2003

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CD26/dipeptidyl peptidase IV (DPPIV) is a surface antigen with multiple functions, including a role in T-cell activation and the development of certain human cancers. We previously demonstrated that CD26/DPPIV enhanced sensitivity of Jurkat cells to doxorubicin. We now show that expression of CD26/DPPIV enhanced sensitivity of CD26 Jurkat transfectants to G 2 -M arrest mediated by the antineoplastic agent etoposide. The increased sensitivity to etoposide-induced G 2 -M arrest was associated with disruption of cell cycle-related events, including hyperphosphorylation of p34 cdc2 kinase, change in cdc25C expression and phosphorylation, and alteration in cyclin B1 expression. CD26/DPPIV-associated enhancement of doxorubicin and etoposideinduced G 2 -M arrest was also observed in serum-free media, suggesting an effect of CD26 on cell-derived processes rather than serum-derived factors. Importantly, our work elucidated a potential mechanism for the enhanced susceptibility of CD26-expressing Jurkat cells to the topoisomerase II inhibitors by demonstrating that CD26/DPPIV surface expression was associated with increased topoisomerase II a levels and enhanced enzyme activity. Besides being the first to show a functional association between the multifaceted molecule CD26 and the key cellular protein topoisomerase II a, our studies provide additional evidence of a potential role for CD26 in the treatment of selected malignancies.

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Direct Association of Adenosine Deaminase with a T Cell Activation Antigen, CD26

Cited by 490 publications

References 33 publications

Transition-State Variation in Human, Bovine, and Plasmodium falciparum Adenosine Deaminases

Transition-State Variation in Human, Bovine, and Plasmodium falciparum Adenosine Deaminases

Adenosine deaminase affects ligand‐induced signalling by interacting with cell surface adenosine receptors

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

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