A Lymphocyte Surface Protein Produces the Signaling Molecule Poly (ADP-ribose) from NAD
Authors
Morrison, Alan R.Faculty Advisor
Rossini, AldoUMass Chan Affiliations
Department of MedicineDocument Type
AbstractPublication Date
2005-06-01Keywords
NADADP Ribose Transferases
Poly(ADP-ribose) Polymerases
Signal Transduction
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
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 websiteDOI
10.1074/jbc.M607259200Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49230Related Resources
Link to article in eScholarshipLink to article in PubMed
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10.1074/jbc.M607259200