A possible role for mono (ADP-ribosyl) transferase in the signalling pathway mediating neutrophil chemotaxis.
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.
Allport
J R
JR
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, UK.
Donnelly
L E
LE
Kefalas
P
P
Lo
G
G
Nunn
A
A
Yadollahi-Farsani
M
M
Rendell
N B
NB
Murray
S
S
Taylor
G W
GW
MacDermot
J
J
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
D000199:Actins; D001704:Biopolymers; D036002:ADP Ribose Transferases; D002118:Calcium