ADENOSINE-DIPHOSPHATE RIBOSYLATION OF FIBROBLAST GROWTH FACTOR-II

Basic fibroblast growth factor (FGF-2) is posttranslationally modified by the enzymatic transfer of ADP-ribose from nicotinamide adenine din ucleotide (NAD), When sonicated nuclei of adrenal capillary endothelia l or SK-Hep1 cells are incubated with [P-32]NAD, FGF-2 is rapidly ADP- ribosylated in a dose- and time-dependent fashion, Proteins structural ly related to FGF-2 (FGF-6 and -7) are readily modified, suggesting th at they share a common substrate motif, Yet, FGF-1, the most structura lly homologous member of the FGF family, is a poor substrate, The reac tion is also specific; interleukin-1 alpha, transforming growth factor -alpha, nerve growth factor, insulin-like growth factor-I, and granulo cyte macrophage-colony stimulating factor are not substrates for ribos ylation. Because the ADP ribosylation of FGF-2 is acid resistant but b ase and hydroxylamine sensitive, the linkage appears to be mediated th rough arginine. Most importantly, however, we also establish that endo genous FGF-2 is a substrate for ribosylation. As such, an immunoreacti ve ADP-ribosylated FGF-2 is detected in extracts of SK-Hep1 nuclei whe n they are incubated with [P-32]NAD, Taken together, these findings su ggest that the role played by ADP ribosylation in signal transduction, DNA repair, the control of the cell cycle, and cell differentiation m ay involve its ability to target molecules such as FGF-2.