Evidence map›Paper›PMID 27136688›Full record

ArticleCell systems2016

Bistability in the Rac1, PAK, and RhoA Signaling Network Drives Actin Cytoskeleton Dynamics and Cell Motility Switches.

Kate M Byrne, Naser Monsefi, John C Dawson, Andrea Degasperi, Jimi-Carlo Bukowski-Wills, Natalia Volinsky, Maciej Dobrzyński, Marc R Birtwistle, Mikhail A Tsyganov, Anatoly Kiyatkin and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Cell systems, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed
12.1field-weighted citation impact, top 1% 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

115 citing papers in PubMed, 185 citations in OpenAlex.

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  15. RABEP1 amplifies front signaling in neutrophil migration.bioRxiv : the preprint server for biology · 2025
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55 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 5 countries.

Kate M ByrneSystems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.
Naser MonsefiSystems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.
John C DawsonEdinburgh Cancer Research Centre, IGMM, University of Edinburgh, Edinburgh EH4 2XR, UK.
Andrea DegasperiSystems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.
Jimi-Carlo Bukowski-WillsEdinburgh Cancer Research Centre, IGMM, University of Edinburgh, Edinburgh EH4 2XR, UK.
Natalia VolinskySystems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.
Maciej DobrzyńskiSystems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.
Marc R BirtwistleDepartment of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Mikhail A TsyganovInstitute of Theoretical and Experimental Biophysics, 142290 Pushchino, Moscow Region, Russia.
Anatoly KiyatkinUniversity of Pennsylvania, Philadelphia, PA 19104, USA.
Katarzyna KidaSystems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.
Andrew J FinchEdinburgh Cancer Research Centre, IGMM, University of Edinburgh, Edinburgh EH4 2XR, UK.
Neil O CarragherEdinburgh Cancer Research Centre, IGMM, University of Edinburgh, Edinburgh EH4 2XR, UK.
Walter KolchSystems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland; Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland; School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
Lan K NguyenSystems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland; Co-senior author; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia. Electronic address: lan.k.nguyen@monash.edu.
Alex von KriegsheimSystems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland; Edinburgh Cancer Research Centre, IGMM, University of Edinburgh, Edinburgh EH4 2XR, UK; Co-senior author; School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address: alex.vonkriegsheim@igmm.ed.ac.uk.
Boris N KholodenkoSystems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland; Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland; School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia.
University College Dublin · IEEdinburgh Cancer Research · GBAustralian Regenerative Medicine Institute · AUIcahn School of Medicine at Mount Sinai · USInstitute of Theoretical and Experimental Biophysics · RUUniversity of Pennsylvania · US

Funding

System Biology Center in New YorkP50GM071558 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI IYENGAR, SRINIVAS RAVI V · 2007 to 2017
$22.8M
Predicting the Heterogeneity of Cell-Fate DecisionsR01GM104184 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BIRTWISTLE, MARC R. · 2014 to 2018
$1.8M
NIGMS NIH HHS P50 GM071558NIGMS NIH HHS R01 GM104184
6 · The paper itself

Abstract

Dynamic interactions between RhoA and Rac1, members of the Rho small GTPase family, play a vital role in the control of cell migration. Using predictive mathematical modeling, mass spectrometry-based quantitation of network components, and experimental validation in MDA-MB-231 mesenchymal breast cancer cells, we show that a network containing Rac1, RhoA, and PAK family kinases can produce bistable, switch-like responses to a graded PAK inhibition. Using a small chemical inhibitor of PAK, we demonstrate that cellular RhoA and Rac1 activation levels respond in a history-dependent, bistable manner to PAK inhibition. Consequently, we show that downstream signaling, actin dynamics, and cell migration also behave in a bistable fashion, displaying switches and hysteresis in response to PAK inhibition. Our results demonstrate that PAK is a critical component in the Rac1-RhoA inhibitory crosstalk that governs bistable GTPase activity, cell morphology, and cell migration switches.

Indexed as

Actin CytoskeletonActinsCell Line, TumorCell MovementCytoskeletonHumansProtein Serine-Threonine Kinasesrac1 GTP-Binding ProteinrhoA GTP-Binding ProteinSignal TransductionActinsProtein Serine-Threonine Kinasesrac1 GTP-Binding ProteinrhoA GTP-Binding Proteinbistable switchescell motilitymathematical modelingPAK inhibitionRac1RhoA

Identifiers

PMID27136688
PMCPMC4802415
OpenAlexW2262060930

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.