Multiple growth factor induction of a murine early response gene that complements a lethal defect in yeast ribosome biogenesis

Identification of the transcriptionally activated targets of receptor tyros ine kinases is critical to understanding biologic programs directing both n ormal and neoplastic growth. To elucidate these molecular processes, we ide ntified genes induced by a potent mesenchymal mitogen, platelet-derived gro wth factor (PDGF), Using differential display reverse transcription-polymer ase chain reaction technology, we isolated a novel growth factor-induced cD NA, San5. San5 transcript induction occurred within 60 min in NIH 3T3 fibro blasts and proceeded in the presence of cycloheximide. Maximal induction of the San5 transcript occurred between 8 and 16 h, concurrent with passage o f fibroblasts through G(1). San5 message was potently induced by PDGF AA an d BB and acidic and basic fibroblast growth factors, all strong activators of fibroblast proliferation, but not by epidermal growth factor and interle ukin-4. In a murine hematopoietic progenitor cell line, San5 transcript ind uction strictly correlated with [H-3]thymidine uptake. Isolation and sequen cing of the murine San5 cDNA revealed amino acid sequence homology to yeast Nop5p, a nucleolar protein required for pre-rRNA processing and ribosome a ssembly. Strikingly, SAN5 was able to rescue a nop5 null mutant, implicatin g SAN5 in the process of ribosome biogenesis. Consistent with this result, SAN5 was localized to the nucleolus in both yeast and mouse. Thus, San5 may provide a link between growth factor receptor activation and the cellular translational machinery.