PXD003213-2

PXD003213 is an original dataset announced via ProteomeXchange.

Title	Bistability in the Rac1, PAK and RhoA signalling network is a feature of cell motility.
Description	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 modelling and experimental validation in MDA-MB-231 mesenchymal breast cancer cells, we show that Rac1 and RhoA interactions via the PAK-family kinases can produce bistable, switch-like responses to a graded PAK inhibition. Using a small chemical inhibitor of PAK we confirm the model conjecture demonstrating that cellular RhoA and Rac activation levels respond in a bistable manner to PAK inhibition where for a given inhibition level these levels are high or low depending on the history of the system. Consequently, we show that downstream signalling, actin dynamics and cell migration also behave in a bistable fashion, displaying abrupt switches and hysteresis in response to PAK inhibition. In summary, our results demonstrate that PAK is a critical component in the Rac1-RhoA inhibitory crosstalk that mediates bistable GTPase activity and cell migration switches.
HostingRepository	PRIDE
AnnounceDate	2017-10-24
AnnouncementXML	Submission_2017-10-24_06:10:56.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex von kriegsheim
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-11-19 01:40:01	ID requested
1	2017-01-03 03:02:31	announced
⏵ 2	2017-10-24 06:10:57	announced	Updated project metadata.
3	2024-10-22 04:26:49	announced	2024-10-22: Updated project metadata.

Byrne KM, Monsefi N, Dawson JC, Degasperi A, Bukowski-Wills JC, Volinsky N, Dobrzy, ń, ski M, Birtwistle MR, Tsyganov MA, Kiyatkin A, Kida K, Finch AJ, Carragher NO, Kolch W, Nguyen LK, von Kriegsheim A, Kholodenko BN, Bistability in the Rac1, PAK, and RhoA Signaling Network Drives Actin Cytoskeleton Dynamics and Cell Motility Switches. Cell Syst, 2(1):38-48(2016) [pubmed]

curator keyword: Biological

submitter keyword: Rac1, RhoA, cell motility, PAK inhibition, bistable switches, mathematical modelling

Alex von Kriegsheim
contact affiliation	University of Edinburgh
contact email	kriegsheim@gmail.com
lab head
Alex von kriegsheim
contact affiliation	Systems Biology
contact email	alex.vonkriegsheim@ucd.ie
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2016/12/PXD003213

PRIDE project URI

• PRIDE
  1. PXD003213
     1. Label: PRIDE project
     2. Name: Bistability in the Rac1, PAK and RhoA signalling network is a feature of cell motility.