TOR and PKA signaling pathways converge on the protein kinase Rim15 to control entry into G0.
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.
Pedruzzi
Ivo
I
Department of Medical Biochemistry, CMU, University of Geneva, 1211 Geneva 4, Switzerland.
Dubouloz
Frédérique
F
Cameroni
Elisabetta
E
Wanke
Valeria
V
Roosen
Johnny
J
Winderickx
Joris
J
De Virgilio
Claudio
C
D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D054648:Protein Phosphatase 2; D016192:Resting Phase, Cell Cycle / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D020123:Sirolimus / Q000378:metabolism
D000935:Antifungal Agents; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose; D019869:Phosphatidylinositol 3-Kinases; D010749:Phosphoprotein Phosphatases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011494:Protein Kinases; D054648:Protein Phosphatase 2; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; C410736:Rim15 protein, S cerevisiae; C083324:TOR1 protein, S cerevisiae; C104343:SIT4 protein, S cerevisiae