Regulation of the cell integrity pathway by rapamycin-sensitive TOR function in budding yeast.
The TOR (target of rapamycin) pathway controls cell growth in response to nutrient availability in eukaryotic cells. Inactivation of TOR function by rapamycin or nutrient exhaustion is accompanied by triggering various cellular mechanisms aimed at overcoming the nutrient stress. Here we report that in Saccharomyces cerevisiae the protein kinase C (PKC)-mediated mitogen-activated protein kinase pathway is regulated by TOR function because upon specific Tor1 and Tor2 inhibition by rapamycin, Mpk1 is activated rapidly in a process mediated by Sit4 and Tap42. Osmotic stabilization of the plasma membrane prevents both Mpk1 activation by rapamycin and the growth defect that occurs upon the simultaneous absence of Tor1 and Mpk1 function, suggesting that, at least partially, TOR inhibition is sensed by the PKC pathway at the cell envelope. This process involves activation of cell surface sensors, Rom2, and downstream elements of the mitogen-activated protein kinase cascade. Rapamycin also induces depolarization of the actin cytoskeleton through the TOR proteins, Sit4 and Tap42, in an osmotically suppressible manner. Finally, we show that entry into stationary phase, a physiological situation of nutrient depletion, also leads to the activation of the PKC pathway, and we provide further evidence demonstrating that Mpk1 is essential for viability once cells enter G(0).
Torres
Jordi
J
Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Lleida 25198, Spain.
Di Como
Charles J
CJ
Herrero
Enrique
E
De La Torre-Ruiz
Maria Angeles
MA
D000199:Actins / Q000502:physiology; D002176:Candida albicans / Q000235:genetics; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*
D000199:Actins; D018797:Cell Cycle Proteins; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011493:Protein Kinase C; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; C083324:TOR1 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae; C072724:SLT2 protein, S cerevisiae