Cell-surface ADP-ribosylation of fibroblast growth factor-2 by an arginine-specific ADP-ribosyltransferase.
Basic fibroblast growth factor (FGF-2) appeared to be ADP-ribosylated on the surface of adult bovine aortic arch endothelial and human hepatoma cells. Further characterization of this reaction with cells expressing an arginine-specific, glycosylphosphatidylinositol-anchored, mono-ADP-ribosyltransferase demonstrated that FGF-2 is ADP-ribosylated on arginine. Incubation of transformed cells with FGF-2 and [adenylate-32P]nicotinamide-adenine dinucleotide (NAD) resulted in the rapid incorporation of [32P]ADP-ribose into FGF-2 in a time- and concentration-dependent manner, with labelling averaging 3 mol of ADP-ribose/mol of FGF-2. Excess ADP-ribose had no effect on these reactions, whereas excess NAD inhibited the ADP-ribosylation of FGF-2, consistent with an enzymic rather than a non-enzymic ADP-ribosylation reaction. Heparin also inhibited the ADP-ribosylation reaction, whereas a neutralizing polyclonal anti-peptide antibody had no effect. Furthermore, the addition of putative receptor binding domain peptide analogues of FGF-2 reduced the maximal ADP-ribosylation of FGF-2. These results identify the cell-surface ADP-ribosylation of FGF-2 as a potentially ubiquitous event.
Jones
E M
EM
Departments of Cell Biology and Vascular Biology, The Scripps Research Institute, 10666 N. Torrey Pines Road, CVN-10, La Jolla, CA 92037, USA.
Baird
A
A
D036002:ADP Ribose Transferases; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002417:Cattle; D004730:Endothelium, Vascular / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013499:Surface Properties; D014407:Tumor Cells, Cultured
D017261:Glycosylphosphatidylinositols; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D000246:Adenosine Diphosphate Ribose; D001120:Arginine; D036002:ADP Ribose Transferases; D011065:Poly(ADP-ribose) Polymerases