title: Molecular characterization of a glycosylphosphatidylinositol-linked ADP-ribosyltransferase from lymphocytes.
abstract: Mono ADP-ribosyltransferases catalyze the transfer of the ADP-ribose moiety of nicotinamide adenine dinucleotide (NAD) to proteins. It was reported by Wang et al (J Immunol 153:4048, 1994) that incubation of mouse cytotoxic T lymphocytes (CTL) with NAD resulted in the ADP-ribosylation of membrane proteins and inhibition of cell proliferation and cytotoxicity. Treatment of CTL with phosphatidylinositol-specific phospholipase C (PI-PLC) before incubation with NAD prevented the inhibitory effects of NAD on the cells, consistent with the removal of a glycosylphosphatidylinositol (GPI)-anchored ADP-ribosyltransferase on the lymphocyte surface. We have identified and cloned a GPI-linked ADP-ribosyltransferase from Yac-1 mouse T-cell lymphoma cells. The deduced amino acid sequence of the Yac-1 transferase was 70% and 41% identical to those of the rabbit skeletal muscle and chicken heterophil, respectively. It contained three noncontiguous sequences similar to those found in several of the bacterial toxin and vertebrate ADP-ribosyltransferases. Based on crystallography of the bacterial toxins, these regions are believed to form, in part, the catalytic site consistent with a common mechanism for the ADP-ribose transfer reaction. In rat mammary adenocarcinoma (NMU) cells transformed with the Yac-1 transferase cDNA, transferase activity was present on the cell surface and was released into the medium by treatment of cells with PI-PLC. Thus, we have cloned a novel gene that has properties identical to the transferase detected in CTL, and may be involved in the NAD-dependent regulation of proliferation and cytotoxicity.
authors.affiliation: Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1434, USA.
authors.forename: I J
authors.initials: IJ
authors.lastname: Okazaki
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: N G
authors.initials: NG
authors.lastname: McElvaney
authors.forename: E
authors.initials: E
authors.lastname: Lesma
authors.forename: J
authors.initials: J
authors.lastname: Moss
mesh_terms: D036002:ADP Ribose Transferases; D000230:Adenocarcinoma / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D001483:Base Sequence; D002645:Chickens; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004790:Enzyme Induction; D019143:Evolution, Molecular; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D016399:Lymphoma, T-Cell / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009243:NAD / Q000502:physiology; D009363:Neoplasm Proteins / Q000235:genetics / Q000302:isolation & purification; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000302:isolation & purification*; D011817:Rabbits; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013601:T-Lymphocytes / Q000201:enzymology*; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D001426:Bacterial Proteins; D018076:DNA, Complementary; D017261:Glycosylphosphatidylinositols; D009363:Neoplasm Proteins; D009243:NAD; D036002:ADP Ribose Transferases; D011065:Poly(ADP-ribose) Polymerases; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase