A cell surface ADP-ribosyltransferase modulates T cell receptor association and signaling.
ART-1, a cell surface ADP-ribosyltransferase, is imbedded in the membrane by a glycosylphosphatidylinositol anchor. Function of this enzyme in mouse T lymphocytes is to transfer ADP-ribose groups from NAD to arginine residues, exposed on the extracellular domain of cell surface molecules. As a consequence, T cell responses are modulated. To explore the precise action of the enzyme, the T cell lymphoma EL-4 was transfected with the ART-1 gene, and its effects were examined. It is shown that ART-1 ADP-ribosylates distinct cell surface molecules, causing inhibition of T cell receptor signaling, concomitant to suppression of p56(lck) kinase activation. These effects are explained by failure of T cell receptors and co-receptors to associate into a contiguous and functional receptor cluster.
Liu
Z X
ZX
Departments of Molecular Microbiology and Immunology, USC/Norris Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles, California 90033, USA.
Yu
Y
Y
Dennert
G
G
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D009243:NAD / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D017261:Glycosylphosphatidylinositols; D007295:Inositol Phosphates; D007376:Interleukin-2; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D009243:NAD; D011065:Poly(ADP-ribose) Polymerases