A possible role for mono(ADP‐ribosyl)transferase in the signalling pathway mediating neutrophil chemotaxis

Allport, Jennifer R.; Donnelly, Louise E.; Kefalas, Panagiotis; Lo, Gar; Nunn, Alistair V.W.; Yadollahi-Farsani, Masoud; Rendell, Nigel B.; Murray, Stephen A.; Taylor, Graham W.; MacDermot, John

doi:10.1046/j.1365-2125.1996.37014.x

Cited by 17 publications

(9 citation statements)

References 11 publications

(13 reference statements)

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“…In addition, we highlight a possible role of ART1 on CD4+CD39+ T cells, which could act as a reservoir of the CD39+ Treg cells (Schuler et al, 2012). These results are in agreement with those described for cytotoxic T lymphocytes and neutrophils (Wang et al, 1994;Allport et al, 1996).…”

Section: Discussionsupporting

confidence: 91%

Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets

et al. 2016

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Section: Discussionsupporting

confidence: 91%

Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets

et al. 2016

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“…ART1, the first cloned and characterized vertebrate ART, is an arginine-specific ADP-ribosyltransferase (3,(5)(6)(7)(8) that is relatively conserved across species with deduced amino acid sequence of the mouse protein 77 and 73% identical to those of the human and rabbit, respectively (9). This cell-surface, GPIanchored protein modifies integrin ␣ 7 in mouse skeletal muscle cells (10).…”

mentioning

confidence: 99%

Identification of Regulatory Domains in ADP-ribosyltransferase-1 That Determine Transferase and NAD Glycohydrolase Activities

Bourgeois

Okazaki

Cavanaugh

et al. 2003

Journal of Biological Chemistry

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Mono-ADP-ribosyltransferases (ART1-7) transfer ADP-ribose from NAD؉ to proteins (transferase activity) or water (NAD glycohydrolase activity). The mature proteins contain two domains, an ␣-helical amino terminus and a ␤-sheet-rich carboxyl terminus. A basic region in the carboxyl termini is encoded in a separate exon in ART1 and ART5. Structural motifs are conserved among ART molecules. Successive amino-or carboxyl-terminal truncations of ART1, an arginine-specific transferase, identified regions that regulated transferase and NAD glycohydrolase activities. In mouse ART1, amino acids 24 -38 (ART-specific extension) were needed to inhibit both activities; amino acids 39 -45 (common ART coil) were required for both. Successive truncations of the ␣-helical region reduced transferase and NAD glycohydrolase activities; however, truncation to residue 106 enhanced both. Removal of the carboxyl-terminal basic domain decreased transferase, but enhanced NAD glycohydrolase, activity. Thus, amino-and carboxyl-terminal regions of ART1 are required for transferase activity. The enhanced glycohydrolase activity of the shorter mutants indicates that sequences, which are not part of the NAD binding, core catalytic site, exert structural constraints, modulating substrate specificity and catalytic activity. These functional domains, defined by discrete exons or structural motifs, are found in ART1 and other ARTs, consistent with conservation of structure and function across the ART family.

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“…A family of mammalian ARTs that are secreted or localized on the cell surface through glycosylphosphatidylinositol anchors (14)(15)(16)(17)(18)(19) are expressed preferentially on epithelial and inflammatory cells such as lymphocytes and neutrophils (17,20). Substrates of the five known mammalian ARTs (ART-1-5) include proteins that are involved in critical cellular events (e.g., lymphocyte activation, neutrophil chemotaxis) (21)(22)(23). Two of these transferases, ART-1 and -5, specifically modify arginine residues in proteins.…”

mentioning

confidence: 99%

ADP ribosylation of human neutrophil peptide-1 regulates its biological properties

Paone

Wada

Stevens

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

116

108

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In human airways, epithelial cells lining the lumen and intraluminal cells (e.g., polymorphonuclear cells) participate in the innate immune response. These cells secrete or express on their surfaces arginine-specific ADP ribosyltransferases. Defensins, antimicrobial proteins secreted by immune cells, are arginine-rich, leading us to hypothesize that ADP ribosylation could modify their biological activities. We found that an arginine-specific ADP ribosyltransferase-1 present on airway epithelial cells modifies Arg-14 of ␣ defensin-1. ADP-ribosylated defensin-1 had decreased antimicrobial and cytotoxic activities but still stimulated T cell chemotaxis and IL-8 release from A549 cells. Further, ADP-ribosylated defensin-1 inhibited cytotoxic and antimicrobial activities of unmodified defensin-1. We identified ADP-ribosylated defensin-1 in bronchoalveolar lavage fluid from smokers but not from nonsmokers, confirming its existence in vivo. Thus, airway mono-ADP-ribosyltransferases could have an important regulatory role in the innate immune response through modification of ␣ defensin-1 and perhaps other basic molecules, with alteration of their biological properties. In the human airway, epithelial cells, in concert with intraluminal cells (e.g., macrophages), contribute to the innate immune response. Activation of airway epithelial cells releases proinflammatory mediators and chemotaxins, leading to the recruitment of inflammatory cells (e.g., neutrophils) (1, 2). Activated neutrophils, in turn, release azurophilic granules that contain human neutrophil peptides (HNP), small cationic peptides ranging in size from 29-33 aa (3). HNPs are characterized by a high arginine content and contain three pairs of disulfidelinked cysteines (4). They have a broad spectrum of antimicrobial and cytotoxic activities and play an important role in the innate immune response against both Gram-positive and -negative bacteria, fungi, and certain enveloped viruses (5-8). High HNP levels have been found in airway secretions of patients with inflammatory lung diseases (9-11).A family of eukaryotic and prokaryotic mono-ADP ribosyltransferases (ARTs) catalyze the transfer of ADP ribose from NAD ϩ to arginine residues in proteins (12). Among the monoARTs are bacterial products (e.g., cholera toxin), which are responsible for the clinical syndrome in disease (13). A family of mammalian ARTs that are secreted or localized on the cell surface through glycosylphosphatidylinositol anchors (14-19) are expressed preferentially on epithelial and inflammatory cells such as lymphocytes and neutrophils (17,20). Substrates of the five known mammalian ARTs (ART-1-5) include proteins that are involved in critical cellular events (e.g., lymphocyte activation, neutrophil chemotaxis) (21-23). Two of these transferases, ART-1 and -5, specifically modify arginine residues in proteins. The finding of ARTs on airway epithelial and inflammatory cells prompted us to evaluate potential substrates for ADP ribosylation in the airway (24). Because of the high arginine c...

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A possible role for mono(ADP‐ribosyl)transferase in the signalling pathway mediating neutrophil chemotaxis

Cited by 17 publications

References 11 publications

Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets

Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets

Identification of Regulatory Domains in ADP-ribosyltransferase-1 That Determine Transferase and NAD Glycohydrolase Activities

ADP ribosylation of human neutrophil peptide-1 regulates its biological properties

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