DISTINCT REPRESSION OF TRANSLATION BY WORTMANNIN AND RAPAMYCIN

The role of phosphatidylinositol 3-kinase and FK506-binding protein ra pamycin associated protein (FRAP) in translational control has been ex amined by treating RD-rhabdomyosarcoma cells with wortmannin and rapam ycin and studying the effects on cell-growth, translation initiation, and protein synthesis. Whereas wortmannin and rapamycin exhibit subtle effects on global translation, examination of individual mRNAs in suc rose gradients and of individual proteins in two-dimensional polyacryl amide gels reveals that wortmannin and rapamycin exhibit distinct effe cts on the translation of individual mRNAs. Wortmannin represses the s ynthesis of a third of cellular proteins, whereas rapamycin affects a subset of these proteins. Since ribosomal protein S6 was rapidly depho sphorylated following wortmannin and rapamycin treatment, and the phos phorylation status of the eukaryotic initiation factor 4E was unchange d, our data imply that the p70 signalling pathway has at least one bra nch-point upstream of FRAP leading to an additional route of translati onal control.