Mechanisms of p130Cas-mediated mechano-sensing in cells

• Applicant: Professor Dr. Ben Fabry
• Subject Area: Biophysics
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 232394966

Adherent cells, when mechanically stressed, show a wide range of responses including large-scale changes in their mechanical behavior and gene expression pattern. This is in part facilitated by activating the focal adhesion protein p130Cas through force-induced conformational changes that subsequently lead to activation of downstream pathways such as extracellular-signal-regulated kinase (ERK1/2) phosphorylation. We have recently demonstrated that the phosphorylation site Y12 on p130Cas modulates the binding with vinculin, which is a prominent mechano-coupling protein in the focal adhesion complex. Preliminary data show that phosphorylation of Y12 or mutation with phospho-mimicking glutamate Y12E suppresses the binding of p130Cas to vinculin, leads to a decline of p130Cas localization in focal adhesions, and to a reduction of stretch-induced p130Cas activation and downstream ERK1/2 signaling. These observations demonstrate that vinculin is an important modulator of the p130Cas-mediated mechano-transduction pathway in cells. The central aim of this project is to test the hypothesis that vinculin is critical for p130Cas incorporation into the focal adhesion complex and for transmitting forces to the p130Cas molecule.

• DFG Programme: Research Grants
• International Connection: Czech Republic
• Partner Organisation: Czech Science Foundation
• Participating Person: Professor Dr. Jan Brabek