Adenosine diphosphate ribosylation of fibroblast growth factor-2.
Basic fibroblast growth factor (FGF-2) is posttranslationally modified by the enzymatic transfer of ADP-ribose from nicotinamide adenine dinucleotide (NAD). When sonicated nuclei of adrenal capillary endothelial or SK-Hep1 cells are incubated with [32P]NAD, FGF-2 is rapidly ADP-ribosylated in a dose- and time-dependent fashion. Proteins structurally related to FGF-2 (FGF-6 and -7) are readily modified, suggesting that they share a common substrate motif. Yet, FGF-1, the most structurally homologous member of the FGF family, is a poor substrate. The reaction is also specific; interleukin-1 alpha, transforming growth factor-alpha, nerve growth factor, insulin-like growth factor-I, and granulocyte macrophage-colony stimulating factor are not substrates for ribosylation. Because the ADP ribosylation of FGF-2 is acid resistant but base and hydroxylamine sensitive, the linkage appears to be mediated through arginine. Most importantly, however, we also establish that endogenous FGF-2 is a substrate for ribosylation. As such, an immunoreactive ADP-ribosylated FGF-2 is detected in extracts of SK-Hep1 nuclei when they are incubated with [32P]NAD. Taken together, these findings suggest that the role played by ADP ribosylation in signal transduction, DNA repair, the control of the cell cycle, and cell differentiation may involve its ability to target molecules such as FGF-2.
Boulle
N
N
Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Jones
E M
EM
Auguste
P
P
Baird
A
A
D000230:Adenocarcinoma / Q000473:pathology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006031:Glycosylation; D006133:Growth Substances / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology; D009243:NAD / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D009243:NAD; D016222:Fibroblast Growth Factor 2; D000246:Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases