Bistability in the Rac1, PAK, and RhoA Signaling Network Drives Actin Cytoskeleton Dynamics and Cell Motility Switches
Files in This Item:
File | Size | Format | |
---|---|---|---|
Download | Bistability in the Rac1, PAK, and RhoA Signaling KholodenkoB.pdf | 2.94 MB | Adobe PDF |
Title: | Bistability in the Rac1, PAK, and RhoA Signaling Network Drives Actin Cytoskeleton Dynamics and Cell Motility Switches | Authors: | Byrne, Kate M.; Monsefi, Naser; Dawson, John C.; Degasperi, Andrea; Volinsky, Natalia; Dobrzyński, Maciej; Kida, Katarzyna; Kolch, Walter; Nguyen, Lan K.; Kriegsheim, Alexander von; Kholodenko, Boris N.; et al. | Permanent link: | http://hdl.handle.net/10197/9760 | Date: | 27-Jan-2016 | Online since: | 2019-04-01T11:20:20Z | 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. | Funding Details: | European Commission - Seventh Framework Programme (FP7) | Funding Details: | SynSignal Breast Cancer NOW |
Type of material: | Journal Article | Publisher: | Elsevier | Journal: | Cell Systems | Volume: | 2 | Issue: | 1 | Start page: | 38 | End page: | 48 | Copyright (published version): | 2016 the Authors | Keywords: | PAK inhibition; Rac1; RhoA; Bistable switches; Cell motility; Mathematical modeling | DOI: | 10.1016/j.cels.2016.01.003 | Language: | en | Status of Item: | Peer reviewed | This item is made available under a Creative Commons License: | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ |
Appears in Collections: | Conway Institute Research Collection SBI Research Collection Medicine Research Collection |
Show full item record
SCOPUSTM
Citations
5
59
Last Week
0
0
Last month
2
2
checked on Sep 12, 2020
Page view(s)
847
Last Week
3
3
Last month
13
13
checked on May 17, 2022
Download(s) 50
288
checked on May 17, 2022
Google ScholarTM
Check
Altmetric
If you are a publisher or author and have copyright concerns for any item, please email research.repository@ucd.ie and the item will be withdrawn immediately. The author or person responsible for depositing the article will be contacted within one business day.