Regulation of Sphingolipid Biosynthesis by the Morphogenesis Checkpoint Kinase Swe1

• Published in: The Journal of biological chemistry Vol. 291; no. 5; pp. 2524 - 2534
• Main Authors: Chauhan, Neha, Han, Gongshe, Somashekarappa, Niranjanakumari, Gable, Kenneth, Dunn, Teresa, Kohlwein, Sepp D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.01.2016; American Society for Biochemistry and Molecular Biology
• Subjects: cell cycle; Cell Cycle Proteins - metabolism; Cell Division; Fatty Acids, Monounsaturated - chemistry; Gene Expression Regulation, Fungal; Glutathione Transferase - metabolism; Glycogen Synthase Kinase 3 - metabolism; Homeostasis; Lipids; metabolic regulation; Mutation; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Serine C-Palmitoyltransferase; serine palmitoyltransferase; sphingolipid; Sphingolipids - biosynthesis; yeast; serine palmitoyltransferase; cell cycle; sphingolipid; phosphorylation; yeast; metabolic regulation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M115.693200

Sphingolipid (SL) biosynthesis is negatively regulated by the highly conserved endoplasmic reticulum-localized Orm family proteins. Defective SL synthesis in Saccharomyces cerevisiae leads to increased phosphorylation and inhibition of Orm proteins by the kinase Ypk1. Here we present evidence that the yeast morphogenesis checkpoint kinase, Swe1, regulates SL biosynthesis independent of the Ypk1 pathway. Deletion of the Swe1 kinase renders mutant cells sensitive to serine palmitoyltransferase inhibition due to impaired sphingoid long-chain base synthesis. Based on these data and previous results, we suggest that Swe1 kinase perceives alterations in SL homeostasis, activates SL synthesis, and may thus represent the missing regulatory link that controls the SL rheostat during the cell cycle.