A Lymphocyte Surface Protein Produces the Signaling Molecule Poly (ADP-ribose) from NAD
Department of Medicine
Moss, Joel; Evans, James; Lambright, David; Greiner, Dale; Mordes, John; Bortell, Rita
Medical Subject Headings
NAD; ADP Ribose Transferases; Poly(ADP-ribose) Polymerases; Signal Transduction
Life Sciences | Medicine and Health Sciences
Elucidation of signaling pathways that prevent immune cells from damaging self-tissue could help target diseases like lupus and juvenile diabetes. Through one such pathway, NAD and its metabolites appear to inhibit T cells of the immune system. NAD is a substrate for two enzyme families that covalently transfer ADP-ribose from NAD to acceptor proteins -- mono-ADP-ribosyl transferases (mARTs) and poly(ADP-ribose) polymerases (PARPs). PARPs distinguish themselves by polymerizing ADP-ribose on the acceptor proteins. Despite differences in amino acid sequences, mARTs and PARPs have similar structural elements in their catalytic cores. Here we report that in the presence of NAD, ART2, a mART and T cell surface protein, forms ADP-ribose polymers on an arginine in a crucial loop of its catalytic core. ART2 appears to be the first hybrid between the mARTs and PARPs, and structural data suggest a mechanism for polymerization activity. The data suggest that signaling with NAD metabolites like ADP-ribose may be a more versatile process than previously recognized, and that molecules like ART2 may have the potential to participate in novel immune cell signaling pathways.
Rights and Permissions
This research was eventually published as follows: Alan R. Morrison, Joel Moss, Linda A. Stevens, James E. Evans, Caitlin Farrell, Eric Merithew, David G. Lambright, Dale L. Greiner, John P. Mordes, Aldo A. Rossini, and Rita Bortell. ART2, a T Cell Surface Mono-ADP-ribosyltransferase, Generates Extracellular Poly(ADP-ribose) J. Biol. Chem. 2006 281: 33363-33372. Link to article on publisher's website
Morrison, Alan R., "A Lymphocyte Surface Protein Produces the Signaling Molecule Poly (ADP-ribose) from NAD" (2005). University of Massachusetts Medical School. Senior Scholars Program. Paper 17.