title: Rat RT6.2 and mouse Rt6 locus 1 are NAD+: arginine ADP ribosyltransferases with auto-ADP ribosylation activity.
abstract: RT6 is a glycosylphosphatidylinositol-linked protein found on the surface of mature rat T lymphocytes. Cells that express RT6 have an immunoregulatory function and modulate the expression of autoimmune diabetes mellitus in the BioBreeding rat. A homologue of the rat RT6 gene, designated Rt6, has been identified in the mouse, but expression of mouse Rt6 protein has not been documented. Rat RT6 is known to be a nicotinamide adenine dinucleotide (NAD+) glycohydrolase. We now report that rat RT6.2 and recombinant mouse Rt6 locus 1 proteins possess auto-ADP ribosylation activity. In addition, mouse Rt6 but not rat RT6, catalyzes the ADP ribosylation of exogenous acceptors such as histones. The ADP-ribosyl-protein bonds in auto-ADP-ribosylated rat RT6.2, auto-ADP-ribosylated mouse Rt6, and ADP-ribosylhistone synthesized by Rt6 were stable to HgCl2 and HCl, but labile to NH2OH, consistent with ADP ribosylarginine linkages. To determine if these enzymatic activities could affect the function of rat T cells, the effect of substrate availability on lymphocyte proliferation was examined. An inverse correlation was observed between NAD+ concentration in the medium and the ability of rat T cells to respond to anti-CD3, ConA, and PMA plus ionomycin. The data suggest that lymphocyte surface ADP ribosyltransferases could be involved in signaling and immunoregulatory processes.
authors.affiliation: The Program in Biomedical Sciences, University of Massachusetts Medical Center, Worcester, MA 01605, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Rigby
authors.forename: R
authors.initials: R
authors.lastname: Bortell
authors.forename: L A
authors.initials: LA
authors.lastname: Stevens
authors.forename: J
authors.initials: J
authors.lastname: Moss
authors.forename: T
authors.initials: T
authors.lastname: Kanaitsuka
authors.forename: H
authors.initials: H
authors.lastname: Shigeta
authors.forename: J P
authors.initials: JP
authors.lastname: Mordes
authors.forename: D L
authors.initials: DL
authors.lastname: Greiner
authors.forename: A A
authors.initials: AA
authors.lastname: Rossini
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D001483:Base Sequence; D003432:Cross-Linking Reagents; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008969:Molecular Sequence Data; D009243:NAD / Q000494:pharmacology; D051381:Rats; D011913:Rats, Inbred BB; D011920:Rats, Inbred WF; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D003432:Cross-Linking Reagents; D017931:DNA Primers; D006649:Histocompatibility Antigens; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D036002:ADP Ribose Transferases; C449322:Art2a protein, mouse; C449339:Art2b protein, mouse; C090163:Art2b protein, rat