Characterization of glycosylphosphatidylinositiol-anchored, secreted, and intracellular vertebrate mono-ADP-ribosyltransferases.
Mono-ADP-ribosylation is a posttranslational modification of proteins in which the ADP-ribose moiety of nicotinamide adenine dinucleotide is transferred to an acceptor amino acid. Five mammalian ADP-ribosyltransferases (ART1--ART5) have been cloned and expression is restricted to tissues such as cardiac and skeletal muscle, leukocytes, brain, and testis. ART1 and ART2 are glycosylphosphatidylinositol (GPI)-anchored ectoenzymes. ART5 appears not to be GPI-linked and may be secreted. In skeletal muscle and lymphocytes, ART1 modifies specific members of the integrin family of adhesion molecules, suggesting that ADP-ribosylation affects cell-matrix or cell-cell interactions. In lymphocytes, ADP-ribosylation of surface proteins is associated with changes in p56lck tyrosine kinase-mediated signaling. The catalytic sites of bacterial toxins and vertebrate transferases have conserved structural features, consistent with a common reaction mechanism. ADP-ribosylation can be reversed by ADP-ribosylarginine hydrolases, resulting in the regeneration of free arginine. Thus, an ADP-ribosylation cycle may play a regulatory role in vertebrate tissues.
Okazaki
I J
IJ
Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1434, USA. Okazaki@gwgate.nhlbi.nih.gov
Moss
J
J
D036002:ADP Ribose Transferases; D000818:Animals; D001717:Birds; D017124:Conserved Sequence; D004791:Enzyme Inhibitors; D006026:Glycoside Hydrolases / Q000737:chemistry / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000378:metabolism*
D004791:Enzyme Inhibitors; D017261:Glycosylphosphatidylinositols; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D036002:ADP Ribose Transferases; D011065:Poly(ADP-ribose) Polymerases; D006026:Glycoside Hydrolases; D009699:N-Glycosyl Hydrolases; C046422:ADP-ribosylarginine hydrolase