ACTIVATION OF RDNA TRANSCRIPTION BY FGF-2 - KEY ROLE OF PROTEIN-KINASE CKII

Basic Fibroblast Growth Factor-2 (FGF-2) promotes G1 to S transition o f quiescent sparse adult bovine aortic endothelial cells. In addition to signal transduction through interaction with tyrosine kinase high a ffinity receptor, FGF-2 is translocated to the nucleus and accumulated into the nucleolus. These data suggest that FGF-2 functions directly in nuclear events. In vivo, correlations were established between the entrance of FGF-2 into the nucleus and an increase in rDNA transcripti on and in protein phosphorylation. In vitro, in experiments carried ou t with nuclei isolated from quiescent cells, addition of FGF-2 increas es rDNA transcription by a factor of 5 and also increases protein phos phorylation. Nucleolin, a factor involved in control of rDNA transcrip tion is preferentially phosphorylated. It has been shown that nucleoli n and other factors implicated in rDNA transcription are substrates of protein kinase CKII. Using purified kinase CKII and nucleolin in an i n vitro phosphorylation assay, we have shown that FGF-2 activates the protein kinase activity. These results suggest that FGF-2 could act as an activator of rDNA transcription through interactions with the prot ein kinase CKII.