title: A possible role for mono (ADP-ribosyl) transferase in the signalling pathway mediating neutrophil chemotaxis.
abstract: 1. Mono(ADP-ribosyl)transferase activity has been identified on the external surface of human polymorphonuclear neutrophil leucocytes (PMNs). The enzyme is released from the plasma membrane by phosphoinositide-specific phospholipase C, suggesting a glycosylphosphatidylinositol (GPI) linkage of the enzyme to the plasma membrane. Partial sequence of cDNA encoding the enzyme suggests that it is identical to the GPI-linked mono(ADP-ribosyl)-transferase identified previously on human skeletal muscle. 2. A panel of inhibitors of mono(ADP-ribosyl)transferase (including vitamins K1 and K3, novobiocin and nicotinamide) showed a rank order of inhibitory potency similar to that described for other mono(ADP-ribosyl)transferases. Furthermore, the mono(ADP-ribosyl)ation of agmatine was inhibited also by diethylamino (benzylidineamino)guanidine (DEA-BAG), another substrate of the enzyme related structurally to arginine. 3. There was a close linear correlation between the IC50 values for inhibition of mono(ADP-ribosyl)ation of agmatine by DEA-BAG or the enzyme inhibitors and their IC50 values for inhibition of receptor-dependent polymerization of cytoskeletal actin and chemotaxis. 4. These results suggest a role for mono(ADP-ribosyl)transferase in the transduction pathway involved in receptor-dependent re-alignment of the cytoskeleton during neutrophil chemotaxis.
authors.affiliation: Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Allport
authors.forename: L E
authors.initials: LE
authors.lastname: Donnelly
authors.forename: P
authors.initials: P
authors.lastname: Kefalas
authors.forename: G
authors.initials: G
authors.lastname: Lo
authors.forename: A
authors.initials: A
authors.lastname: Nunn
authors.forename: M
authors.initials: M
authors.lastname: Yadollahi-Farsani
authors.forename: N B
authors.initials: NB
authors.lastname: Rendell
authors.forename: S
authors.initials: S
authors.lastname: Murray
authors.forename: G W
authors.initials: GW
authors.lastname: Taylor
authors.forename: J
authors.initials: J
authors.lastname: MacDermot
mesh_terms: D036002:ADP Ribose Transferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D001704:Biopolymers; D002118:Calcium / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D006801:Humans; D015398:Signal Transduction
chemical_list: D000199:Actins; D001704:Biopolymers; D036002:ADP Ribose Transferases; D002118:Calcium