TOR and PKA Signaling Pathways Converge on the Protein Kinase Rim15 to Control Entry into G 0

Abstract

The highly conserved Tor kinases (TOR) and the protein kinase A (PKA) pathway regulate cell proliferation in response to growth factors and/or nutrients. In Saccharomyces cerevisiae, loss of either TOR or PKA causes cells to arrest growth early in G 1 and to enter G 0 by mechanisms that are poorly understood. Here we demonstrate that the protein kinase Rim15 is required for entry into G 0 following inactivation of TOR and/or PKA. Induction of Rim15-dependent G 0 traits requires two discrete processes, i.e., nuclear accumulation of Rim15, which is negatively regulated both by a Sit4-independent TOR effector branch and the protein kinase B (PKB/Akt) homolog Sch9, and release from PKA-mediated inhibition of its protein kinase activity. Thus, Rim15 integrates signals from at least three nutrient-sensory kinases (TOR, PKA, and Sch9) to properly control entry into G 0, a key developmental process in eukaryotic cells.