Showing papers by "Friedrich Koch-Nolte published in 2003"
TL;DR: These results delineate an alternative mechanism for inducing T cell death and set an interesting precedent for immunoregulation via crosstalk between NAD-dependent ADP-ribosyltransferases and purinoceptors.
320 citations
TL;DR: In this paper, 1G4 is used to detect ADP-ribosylation of cell surface proteins on living cells by exploiting the capacity of ARTs to utilize etheno-NAD as substrate.
48 citations
TL;DR: The data constitute the first analysis of subcellular Ca(2+) signals in T cells and indicate that the pacemaker Ca( 2+) release events, which are necessary for the development of the global Ca(1+) signal, are composed of Ca(3+) release both from inositol 1,4,5-trisphosphate- and ryanodine receptors.
34 citations
TL;DR: The structures and mutant activities of ecto-ADP-ribosyltransferase 2.2 from rat and to its mutants E189I and E189A have been established, confirming that hydrolysis is the major function of this enzyme.
Abstract: The structures of beta-methylenethiazole-4-carboxamide adenine dinucleotide (TAD), NAD(+), and NADH as bound to ecto-ADP-ribosyltransferase 2.2 from rat and to its mutants E189I and E189A, respectively, have been established. The positions and conformations of NAD(+) and its analogues agree in general with those in other ADP-ribosyltransferases. The kinetic constants for NAD(+) hydrolysis were determined by RP-HPLC. The specific activity amounts to 26 units/mg, which is 6000-fold higher than a previously reported rate and 500-fold higher than the hydrolysis rates of other ADP-ribosyltransferases, confirming that hydrolysis is the major function of this enzyme. On the basis of structures and mutant activities, a catalytic mechanism is proposed. The known auto-ADP-ribosylation of the enzyme at the suggested position R184 is supported by one of the crystal structures where the nucleophile position is occupied by an Neta atom of this arginine which in turn is backed up by the base E159.
32 citations
TL;DR: This alternative pathway to T cell apoptosis could be triggered upon the release of NAD from intracellular stores, for example, during inflammatory tissue damage.
Abstract: Cytotoxicity induced by protein ADP-ribosylation is a common theme of certain bacterial toxins and of the mammalian ectoenzyme ART2. Exposure of T cells to NAD, the substrate for ART2-catalyzed ADP-ribosylation, induces exposure of phosphatidylserine, uptake of propidium iodide, and fragmentation of DNA. ART2-specific antibodies raised by gene gun immunization block NAD-induced apoptosis. ART2 catalyzed ADP-ribosylation of cell membrane proteins induces formation of cytolytic membrane pores by activating the P2X7 purinoceptor. This alternative pathway to T cell apoptosis could be triggered upon the release of NAD from intracellular stores, for example, during inflammatory tissue damage.
16 citations
TL;DR: The LKLF gene is not defective in dpBB rats and that its expression is not compromised by the lyp mutation, which has recently been identified as immune‐associated nucleotide 4 (ian4).
Abstract: Diabetes-prone BB (dpBB) rats develop autoimmune insulin-dependent diabetes mellitus (IDDM) at high frequency as a consequence of a defect in T cell development, caused by a mutation in a single gene locus on rat chromosome 4 (lyp) which has recently been identified as immune-associated nucleotide 4 (ian4). A phenotype similar to dpBB rat lymphopenia has recently been described in the mouse as the result of the targeted inactivation of the gene for the transcription factor LKLF (Lung Kruppel-like factor, KLF2) in the immune system. We cloned the LKLF gene of the rat and screened a panel of rat/hamster radiation hybrid cell lines to determine its chromosomal localization. We conclude that the LKLF gene is not defective in dpBB rats and that its expression is not compromised by the lyp mutation.
6 citations
Patent•
22 Jul 2003
TL;DR: The use of at least one NAD analogue, mono-ADP-ribosyl transferase substrate and NAD antagonist, for preparing a medicine designed to modulate the activity of a purinergic receptor, advantageously of type P2X or P2Y.
Abstract: The invention concerns the use of at least one NAD analogue, mono-ADP-ribosyl transferase substrate and NAD antagonist, for preparing a medicine designed to modulate the activity of at least one purinergic receptor, advantageously of type P2X or P2Y, said medicine being particularly designed to treat pathologies wherein purinergic receptors are involved in the physiopathological process or pathologies related to deregulation of the activity of purinergic receptors.