Evidence map›Paper›PMID 25279700›Full record

ArticleeLife2014

TORC2-dependent protein kinase Ypk1 phosphorylates ceramide synthase to stimulate synthesis of complex sphingolipids.

Alexander Muir, Subramaniam Ramachandran, Françoise M Roelants, Garrett Timmons, Jeremy Thorner

Open access · goldAbstract read
In one paragraph

Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed
8.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

101 citing papers in PubMed, 178 citations in OpenAlex.

  1. Article
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  5. bioRxiv : the preprint server for biology · 2025
    Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Structure of the yeast ceramide synthase.Nature structural & molecular biology · 2025
    Article
  11. Article
  12. Review
  13. Article
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  15. Article
  16. Article
  17. Article
  18. The Implication of Sphingolipids in Viral Infections.International journal of molecular sciences · 2023
    Review
  19. Review
  20. Article

41 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Alexander MuirDivision of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Subramaniam RamachandranDivision of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Françoise M RoelantsDivision of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Garrett TimmonsDepartment of Chemistry, University of California, Berkeley, Berkeley, United States.
Jeremy ThornerDivision of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
University of California, Berkeley · US

Funding

THE MOLECULAR BASIS OF CELL FUNCTIONT32GM007232 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI BILDER, DAVID, UNAL, ELCIN · 1985 to 2022
$36.4M
Yeast Protein Kinase Signaling Networks: Specificity, Regulation and FunctionR01GM021841 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI THORNER, JEREMY W. · 1985 to 2019
$11.8M
Mechanistic Studies of EGFR/ErbB Receptor Tyrosine KinasesR01GM099092 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COLE, PHILIP A, LEAHY, DANIEL J · 2012 to 2015
$1.2M
NIGMS NIH HHS GM099092NIGMS NIH HHS R01 GM021841NIGMS NIH HHS R01 GM21841NIGMS NIH HHS T32 GM007232
6 · The paper itself

Abstract

Plasma membrane lipid composition must be maintained during growth and under environmental insult. In yeast, signaling mediated by TOR Complex 2 (TORC2)-dependent protein kinase Ypk1 controls lipid abundance and distribution in response to membrane stress. Ypk1, among other actions, alleviates negative regulation of L-serine:palmitoyl-CoA acyltransferase, upregulating production of long-chain base precursors to sphingolipids. To explore other roles for TORC2-Ypk1 signaling in membrane homeostasis, we devised a three-tiered genome-wide screen to identify additional Ypk1 substrates, which pinpointed both catalytic subunits of the ceramide synthase complex. Ypk1-dependent phosphorylation of both proteins increased upon either sphingolipid depletion or heat shock and was important for cell survival. Sphingolipidomics, other biochemical measurements and genetic analysis demonstrated that these modifications of ceramide synthase increased its specific activity and stimulated channeling of long-chain base precursors into sphingolipid end-products. Control at this branch point also prevents accumulation of intermediates that could compromise cell growth by stimulating autophagy.

Indexed as

AutophagyCalcineurinCell SurvivalDown-RegulationGlycogen Synthase Kinase 3Heat-Shock ResponseMechanistic Target of Rapamycin Complex 2Membrane ProteinsModels, BiologicalMultiprotein ComplexesOxidoreductasesPhosphorylationPhosphoserineSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSignal TransductionCalcineurindihydroceramide desaturaseGlycogen Synthase Kinase 3LAC1 protein, S cerevisiaeLAG1 protein, S cerevisiaeMCK1 protein, S cerevisiaeMechanistic Target of Rapamycin Complex 2Membrane ProteinsMultiprotein ComplexesOxidoreductasesPhosphoserineSaccharomyces cerevisiae ProteinsSphingolipidsTOR Serine-Threonine Kinasesbiochemistrycell biologylipidsmutantsphosphorylationplasma membraneregulationS. cerevisiaesubstrates

Identifiers

PMID25279700
PMCPMC4217029
OpenAlexW2103370167

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.