AI Article Synopsis
- Dynamic interactions between RhoA and Rac1 are essential for cell migration control in cancer cells.
- Using advanced techniques, researchers found that variations in PAK inhibition lead to bistable responses from these proteins, affecting cell behavior.
- PAK plays a crucial role in mediating how RhoA and Rac1 interact, influencing cell shape and migration through switch-like behavior in response to changes in PAK levels.
Article 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802415 | PMC |
| http://dx.doi.org/10.1016/j.cels.2016.01.003 | DOI Listing |
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