Tor and Cyclic AMP-Protein Kinase A: Two Parallel Pathways Regulating Expression of Genes Required for Cell Growth

Abstract

ABSTRACT In the budding yeast Saccharomyces cerevisiae , the Tor and cyclic AMP-protein kinase A (cAMP-PKA) signaling cascades respond to nutrients and regulate coordinately the expression of genes required for cell growth, including ribosomal protein (RP) and stress-responsive (STRE) genes. The inhibition of Tor signaling by rapamycin results in repression of the RP genes and induction of the STRE genes. Mutations that hyperactivate PKA signaling confer resistance to rapamycin and suppress the repression of RP genes imposed by rapamycin. By contrast, partial inactivation of PKA confers rapamycin hypersensitivity but only modestly affects RP gene expression. Complete inactivation of PKA impairs RP gene expression and concomitantly enhances STRE gene expression; remarkably, this altered transcriptional pattern is still sensitive to rapamycin and thus subject to Tor control. These findings illustrate how the Tor and cAMP-PKA signaling pathways respond to nutrient signals to govern gene expression required for cell growth via two parallel routes, and they have broad implication for our understanding of analogous regulatory networks in normal and neoplastic mammalian cells.