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Sphingolipid profiling indicates that sch9\u0394 cells have increased levels of long-chain bases and long-chain base-1 phosphates, decreased levels of several species of (phyto)ceramides, and altered ratios of complex sphingolipids. We show that the target of rapamycin complex 1\u2013Sch9 signaling pathway functions to repress the expression of the ceramidase genes YDC1 and YPC1, thereby revealing, for the first time in yeast, a nutrient-dependent transcriptional mechanism involved in the regulation of sphingolipid metabolism. In addition, we establish that Sch9 affects the activity of the inositol phosphosphingolipid phospholipase C, Isc1, which is required for ceramide production by hydrolysis of complex sphingolipids. Given that sphingolipid metabolites play a crucial role in the regulation of stress tolerance and longevity of yeast cells, our data provide a model in which Sch9 regulates the latter phenotypes by acting not only as an effector but also as a regulator of sphingolipid metabolism.<\/jats:p>","DOI":"10.1091\/mbc.e13-06-0340","type":"journal-article","created":{"date-parts":[[2013,11,7]],"date-time":"2013-11-07T04:32:56Z","timestamp":1383798776000},"page":"196-211","source":"Crossref","is-referenced-by-count":67,"title":["The protein kinase Sch9 is a key regulator of sphingolipid metabolism in<i>Saccharomyces cerevisiae<\/i>"],"prefix":"10.1091","volume":"25","author":[{"given":"Erwin","family":"Swinnen","sequence":"first","affiliation":[{"name":"Functional Biology, KU Leuven, 3001 Heverlee, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Wilms","sequence":"additional","affiliation":[{"name":"Functional Biology, KU Leuven, 3001 Heverlee, 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