biostudies-literatureAronova SNIEHS NIH HHSNIGMS NIH HHS148-58https://www.ebi.ac.uk/biostudies/studies/S-EPMC3882310biostudies-literatureUnknown7(2)Ceramides and sphingoid long-chain bases (LCBs) are precursors to more complex sphingolipids and play distinct signaling roles crucial for cell growth and survival. Conserved reactions within the sphingolipid biosynthetic pathway are responsible for the formation of these intermediates. Components of target of rapamycin complex 2 (TORC2) have been implicated in the biosynthesis of sphingolipids in S. cerevisiae; however, the precise step regulated by this complex remains unknown. Here we demonstrate that yeast cells deficient in TORC2 activity are impaired for de novo ceramide biosynthesis both in vivo and in vitro. We find that TORC2 regulates this step in part by activating the AGC kinase Ypk2 and that this step is antagonized by the Ca2+/calmodulin-dependent phosphatase calcineurin. BecCell metabolismRegulation of ceramide biosynthesis by TOR complex 2.PMC3882310T32 ES007059R37 ES02710R01 GM086387P30 ES005707P30 ES05707R37 ES002710P42 ES004699Wedaman KRamos KFontes KPowers TAronov PAAronova SHammock BDfalseRegulation of ceramide biosynthesis by TOR complex 2.Ceramides and sphingoid long-chain bases (LCBs) are precursors to more complex sphingolipids and play distinct signaling roles crucial for cell growth and survival. Conserved reactions within the sphingolipid biosynthetic pathway are responsible for the formation of these intermediates. Components of target of rapamycin complex 2 (TORC2) have been implicated in the biosynthesis of sphingolipids in S. cerevisiae; however, the precise step regulated by this complex remains unknown. Here we demonstrate that yeast cells deficient in TORC2 activity are impaired for de novo ceramide biosynthesis both in vivo and in vitro. We find that TORC2 regulates this step in part by activating the AGC kinase Ypk2 and that this step is antagonized by the Ca2+/calmodulin-dependent phosphatase calcineurin. Bec2008-01-01T00:00:00Z2008 Feb2025-04-22T19:31:26.957Z2019-03-27T01:19:27ZS-EPMC38823101824917410.1016/j.cmet.2007.11.015