Molecular cloning and characterization of lymphocyte and muscle ADP-ribosyltransferases.
Mono-ADP-ribosylation, catalyzed by ADP-ribosyltransferases, is a posttranslational modification of proteins in which the ADP-ribose moiety of NAD is transferred to an acceptor protein(arginine). Several of the bacterial toxin ADP-ribosyltransferases have been well characterized in their ability to alter cellular metabolism. It has been postulated that these bacterial toxins mimic the actions of transferases from mammalian cells. We have cloned and characterized ADP-ribosyltransferases from rabbit and human skeletal muscle, and mouse lymphocytes. The muscle transferases are glycosylphosphatidylinositol (GPI)-anchored proteins that are conserved among species. Two distinct transferases, termed Yac-1 and Yac-2 were cloned from mouse lymphoma (Yac-1) cells. The Yac-1 transferase, like the muscle enzymes, is a GPI-linked exoenzyme. The Yac-2 transferase, on the other hand, is membrane-associated but appears not to be GPI-linked. In contrast to Yac-1, the Yac-2 enzyme had significant NAD glycohydrolase activity and may preferentially hydrolyze NAD. The bacterial toxin ADP-ribosyltransferases contain three noncontiguous regions of sequence similarity, which are involved in formation of the catalytic site. Alignment of the deduced amino acid sequences of the mammalian transferases and the rodent RT6 enzymes, along with results from site-directed mutagenesis of the muscle enzyme, are consistent with the notion of a common mechanism of NAD binding and catalysis among ADP-ribosyltransferases.
Okazaki
I J
IJ
Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kim
H J
HJ
Moss
J
J
D036002:ADP Ribose Transferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003001:Cloning, Molecular; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology*; D051379:Mice; D018482:Muscle, Skeletal / Q000201:enzymology*; D011817:Rabbits; D014407:Tumor Cells, Cultured
D017261:Glycosylphosphatidylinositols; D036002:ADP Ribose Transferases