Plasma membrane proteins Slm1 and Slm2 mediate activation of the AGC kinase Ypk1 by TORC2 and sphingolipids in S. cerevisiae.
The PH domain-containing proteins Slm1 and Slm2 were originally identified as substrates of the rapamycin-insensitive TOR complex 2 (TORC2) and as mediators of signaling by the lipid second messenger phosphatidyl-inositol-4,5-bisphosphate (PI4,5P2) in budding yeast S. cerevisiae. More recently, these proteins have been identified as critical effectors that facilitate phosphorylation and activation of the AGC kinases Ypk1 and Ypk2 by TORC2. Here, we review the molecular basis for this regulation as well as place it within the context of recent findings that have revealed Slm1/2 and TORC2-dependent phosphorylation of Ypk1 is coupled to the biosynthesis of complex sphingolipids and to their levels within the plasma membrane (PM) as well as other forms of PM stress. Together, these studies reveal the existence of an intricate homeostatic feedback mechanism, whereby the activity of these signaling components is linked to the biosynthesis of PM lipids according to cellular need.
Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, CA, USA.
Brad J
BJ
Niles
Ted
T
Powers
D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004789:Enzyme Activation; D025461:Feedback, Physiological; D015966:Gene Expression Regulation, Fungal; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013107:Sphingolipids / Q000096:biosynthesis*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D046912:Multiprotein Complexes; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C502930:Slm1 protein, S cerevisiae; C502931:Slm2 protein, S cerevisiae; D013107:Sphingolipids; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; C068124:MCK1 protein, S cerevisiae