Evidence map›Paper›PMID 26246599›Full record

ArticleMolecular biology of the cell2015

Phosphorylation-dependent inhibition of Cdc42 GEF Gef1 by 14-3-3 protein Rad24 spatially regulates Cdc42 GTPase activity and oscillatory dynamics during cell morphogenesis.

Maitreyi Das, Illyce Nuñez, Marbelys Rodriguez, David J Wiley, Juan Rodriguez, Ali Sarkeshik, John R Yates, Peter Buchwald, Fulvia Verde

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

31 citing papers in PubMed, 51 citations in OpenAlex.

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  12. Label-Free Quantitative Phosphoproteomics of the Fission YeastInternational journal of molecular sciences · 2021
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  19. Rho Family GTPases in Fission Yeast Cytokinesis.Communicative & integrative biology · 2019
    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

9 authors at 3 institutions in 1 country.

Maitreyi DasDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33101.
Illyce NuñezDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33101.
Marbelys RodriguezDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33101.
David J WileyDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33101.
Juan RodriguezDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33101.
Ali SarkeshikDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33101.
John R YatesDepartment of Chemical Physiology, Scripps Research Institute, La Jolla, CA 92037.
Peter BuchwaldDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33101.
Fulvia VerdeDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33101 Marine Biological Laboratory, Woods Hole, MA 02543. fverde@med.miami.edu).
University of Miami · USScripps Research Institute · USWoodwell Climate Research Center · US

Funding

TrainingP41GM103533 · NIGMS · UNIVERSITY OF WASHINGTON · PI MACCOSS, MICHAEL · 2012 to 2021
$20.7M
Quantitative Proteome Analysis of Brain DevelopmentR01MH067880 · NIMH · SCRIPPS RESEARCH INSTITUTE, THE · PI YATES III, JOHN R · 2003 to 2017
$7.1M
Control of cell morphogenesis and cell growth by conserved NDR kinase Orb6R01GM095867 · NIGMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI VERDE, FULVIA · 2011 to 2015
$1.4M
NIGMS NIH HHS GM095867NIGMS NIH HHS P41 GM103533NIGMS NIH HHS R01 GM095867NIMH NIH HHS R01 MH 067880NIMH NIH HHS R01 MH067880
6 · The paper itself

Abstract

Active Cdc42 GTPase, a key regulator of cell polarity, displays oscillatory dynamics that are anticorrelated at the two cell tips in fission yeast. Anticorrelation suggests competition for active Cdc42 or for its effectors. Here we show how 14-3-3 protein Rad24 associates with Cdc42 guanine exchange factor (GEF) Gef1, limiting Gef1 availability to promote Cdc42 activation. Phosphorylation of Gef1 by conserved NDR kinase Orb6 promotes Gef1 binding to Rad24. Loss of Rad24-Gef1 interaction increases Gef1 protein localization and Cdc42 activation at the cell tips and reduces the anticorrelation of active Cdc42 oscillations. Increased Cdc42 activation promotes precocious bipolar growth activation, bypassing the normal requirement for an intact microtubule cytoskeleton and for microtubule-dependent polarity landmark Tea4-PP1. Further, increased Cdc42 activation by Gef1 widens cell diameter and alters tip curvature, countering the effects of Cdc42 GTPase-activating protein Rga4. The respective levels of Gef1 and Rga4 proteins at the membrane define dynamically the growing area at each cell tip. Our findings show how the 14-3-3 protein Rad24 modulates the availability of Cdc42 GEF Gef1, a homologue of mammalian Cdc42 GEF DNMBP/TUBA, to spatially control Cdc42 GTPase activity and promote cell polarization and cell shape emergence.

Indexed as

cdc42 GTP-Binding Proteincdc42 GTP-Binding Protein, Saccharomyces cerevisiaeCell Cycle ProteinsCell PolarityCell ShapeChloride ChannelsCytoskeletonGTP PhosphohydrolasesGuanine Nucleotide Exchange FactorsIntracellular Signaling Peptides and ProteinsMicrotubulesPhosphorylationProtein Serine-Threonine KinasesSaccharomyces cerevisiae ProteinsSchizosaccharomycesSchizosaccharomyces pombe Proteinscdc42 GTP-Binding Proteincdc42 GTP-Binding Protein, Saccharomyces cerevisiaeCell Cycle ProteinsChloride ChannelsGEF1 protein, S cerevisiaeGTP PhosphohydrolasesGuanine Nucleotide Exchange FactorsIntracellular Signaling Peptides and ProteinsOrb6 protein, S pombeProtein Serine-Threonine KinasesRAD24 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsSchizosaccharomyces pombe Proteins

Identifiers

PMID26246599
PMCPMC4591695
OpenAlexW1910875386

What OpenQuestion holds

Textmetadata
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.