Evidence map›Paper›PMID 24631237›Full record

ArticleCurrent biology : CB2014

Inhibitory GEF phosphorylation provides negative feedback in the yeast polarity circuit.

Chun-Chen Kuo, Natasha S Savage, Hsin Chen, Chi-Fang Wu, Trevin R Zyla, Daniel J Lew

Open access · bronzeAbstract read
In one paragraph

Article in Current biology : CB, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

46 citing papers in PubMed, 93 citations in OpenAlex.

  1. Polarization as a Process: The Potential of Process Ontology for Understanding Cellular Symmetry Breaking.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
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  7. Patterning of the cell cortex by Rho GTPases.Nature reviews. Molecular cell biology · 2024
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Orientation of Cell Polarity by Chemical Gradients.Annual review of biophysics · 2022
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article
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

6 authors at 3 institutions in 2 countries.

Chun-Chen KuoDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Natasha S SavageInstitute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK.
Hsin ChenDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Chi-Fang WuDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Trevin R ZylaDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Daniel J LewDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: daniel.lew@duke.edu.
Duke Medical Center · USDuke University · USUniversity of Liverpool · GB

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8M
POLARITY ESTABLISHMENT IN YEASTR01GM062300 · NIGMS · DUKE UNIVERSITY · PI LEW, DANIEL J · 2001 to 2016
$5.0M
NCI NIH HHS P30 CA014236NIGMS NIH HHS GM62300NIGMS NIH HHS R01 GM062300Wellcome Trust
6 · The paper itself

Abstract

Cell polarity is critical for the form and function of many cell types. During polarity establishment, cells define a cortical "front" that behaves differently from the rest of the cortex. The front accumulates high levels of the active form of a polarity-determining Rho-family GTPase (Cdc42, Rac, or Rop) that then orients cytoskeletal elements through various effectors to generate the polarized morphology appropriate to the particular cell type [1, 2]. GTPase accumulation is thought to involve positive feedback, such that active GTPase promotes further delivery and/or activation of more GTPase in its vicinity [3]. Recent studies suggest that once a front forms, the concentration of polarity factors at the front can increase and decrease periodically, first clustering the factors at the cortex and then dispersing them back to the cytoplasm [4-7]. Such oscillatory behavior implies the presence of negative feedback in the polarity circuit [8], but the mechanism of negative feedback was not known. Here we show that, in the budding yeast Saccharomyces cerevisiae, the catalytic activity of the Cdc42-directed GEF is inhibited by Cdc42-stimulated effector kinases, thus providing negative feedback. We further show that replacing the GEF with a phosphosite mutant GEF abolishes oscillations and leads to the accumulation of excess GTP-Cdc42 and other polarity factors at the front. These findings reveal a mechanism for negative feedback and suggest that the function of negative feedback via GEF inhibition is to buffer the level of Cdc42 at the polarity site.

Indexed as

Cell Polaritycdc42 GTP-Binding Protein, Saccharomyces cerevisiaeComputer SimulationFeedback, PhysiologicalGuanine Nucleotide Exchange FactorsModels, BiologicalPhosphorylationSaccharomyces cerevisiaeSignal Transductioncdc42 GTP-Binding Protein, Saccharomyces cerevisiaeGuanine Nucleotide Exchange Factors

Identifiers

PMID24631237
PMCPMC4018745
OpenAlexW2008619055

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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.