Evidence map›Paper›PMID 22535525›Full record

ArticleMolecular biology of the cell2012

Orm protein phosphoregulation mediates transient sphingolipid biosynthesis response to heat stress via the Pkh-Ypk and Cdc55-PP2A pathways.

Yidi Sun, Yansong Miao, Yukari Yamane, Chao Zhang, Kevan M Shokat, Hiromu Takematsu, Yasunori Kozutsumi, David G Drubin

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
6.6field-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

91 citing papers in PubMed, 139 citations in OpenAlex.

  1. Article
  2. ORMDL Proteins Turnover via Proteasome and Autophagy Is Cell-Type Dependent and Tied to Ceramide Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  3. Review
  4. Review
  5. Regulation of cellular and systemic sphingolipid homeostasis.Nature reviews. Molecular cell biology · 2024
    Review
  6. Article
  7. Review
  8. Inducible degradation-coupled phosphoproteomics identifies PP2AFrontiers in cell and developmental biology · 2024
    Article
  9. The Implication of Sphingolipids in Viral Infections.International journal of molecular sciences · 2023
    Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. De Novo Sphingolipid Biosynthesis in Atherosclerosis.Advances in experimental medicine and biology · 2022
    Article
  17. Review
  18. Article
  19. Review
  20. Article

31 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

8 authors at 3 institutions in 2 countries.

Yidi SunDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Yansong Miao
Yukari Yamane
Chao Zhang
Kevan M Shokat
Hiromu Takematsu
Yasunori Kozutsumi
David G Drubin
Kyoto University · JPUniversity of California, Berkeley · USUniversity of California, San Francisco · US

Funding

The budding yeast endocytic pathwayR01GM050399 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI DRUBIN, DAVID G · 1997 to 2015
$5.9M
NIGMS NIH HHS R01 GM050399NIGMS NIH HHS R01 GM 50399
6 · The paper itself

Abstract

Sphingoid intermediates accumulate in response to a variety of stresses, including heat, and trigger cellular responses. However, the mechanism by which stress affects sphingolipid biosynthesis has yet to be identified. Recent studies in yeast suggest that sphingolipid biosynthesis is regulated through phosphorylation of the Orm proteins, which in humans are potential risk factors for childhood asthma. Here we demonstrate that Orm phosphorylation status is highly responsive to sphingoid bases. We also demonstrate, by monitoring temporal changes in Orm phosphorylation and sphingoid base production in cells inhibited for yeast protein kinase 1 (Ypk1) activity, that Ypk1 transmits heat stress signals to the sphingolipid biosynthesis pathway via Orm phosphorylation. Our data indicate that heat-induced sphingolipid biosynthesis in turn triggers Orm protein dephosphorylation, making the induction transient. We identified Cdc55-protein phosphatase 2A (PP2A) as a key phosphatase that counteracts Ypk1 activity in Orm-mediated sphingolipid biosynthesis regulation. In total, our study reveals a mechanism through which the conserved Pkh-Ypk kinase cascade and Cdc55-PP2A facilitate rapid, transient sphingolipid production in response to heat stress through Orm protein phosphoregulation. We propose that this mechanism serves as the basis for how Orm phosphoregulation controls sphingolipid biosynthesis in response to stress in a kinetically coupled manner.

Indexed as

Hot TemperatureSignal Transduction3-Phosphoinositide-Dependent Protein KinasesBlotting, WesternCell Cycle ProteinsGlycogen Synthase Kinase 3Models, BiologicalMutationPhosphorylationProtein KinasesProtein Phosphatase 2Protein Serine-Threonine KinasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSphingolipidsSphingosine3-Phosphoinositide-Dependent Protein KinasesCDC55 protein, S cerevisiaeCell Cycle ProteinsGlycogen Synthase Kinase 3MCK1 protein, S cerevisiaeOrm1 protein, S cerevisiaeOrm2 protein, S cerevisiaePKH1 protein, S cerevisiaePKH2 protein, S cerevisiaeProtein KinasesProtein Phosphatase 2Protein Serine-Threonine KinasesSaccharomyces cerevisiae ProteinssafingolSphingolipidsSphingosineYPK2 protein, S cerevisiae

Identifiers

PMID22535525
PMCPMC3374756
OpenAlexW2139292247

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.