Journal
CELL SYSTEMS
Volume 2, Issue 1, Pages 38-48Publisher
CELL PRESS
DOI: 10.1016/j.cels.2016.01.003
Keywords
-
Categories
Funding
- EU Seventh Framework under project PRIMES [FP7-278568]
- EU Seventh Framework under project SynSignal [613879]
- EU Seventh Framework under project Breast Cancer NOW [2013NovPR183]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available