FAK controls the mechanical activation of YAP, a transcriptional regulator required for durotaxis

FASEB J. 2018 Feb;32(2):1099-1107. doi: 10.1096/fj.201700721R. Epub 2018 Jan 3.

Abstract

Focal adhesion kinase (FAK) is a key molecule in focal adhesions and regulates fundamental processes in cells such as growth, survival, and migration. FAK is one of the first molecules recruited to focal adhesions in response to external mechanical stimuli and therefore is a pivotal mediator of cell mechanosignaling, and relays these stimuli to other mechanotransducers within the cytoplasm. Yes-associated protein (YAP) has been identified recently as one of these core mechanotransducers. YAP translocates to the nucleus following changes in cell mechanics to promote the expression of genes implicated in motility, apoptosis, proliferation, and organ growth. Here, we show that FAK controls the nuclear translocation and activation of YAP in response to mechanical activation and submit that the YAP-dependent process of durotaxis requires a cell with an asymmetric distribution of active and inactive FAK molecules.-Lachowski, D., Cortes, E., Robinson, B., Rice, A., Rombouts, K., Del Río Hernández, A. E. FAK controls the mechanical activation of YAP, a transcriptional regulator required for durotaxis.

Keywords: directed migration; focal adhesions; mechanotransduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis / genetics
  • Cell Movement*
  • Cell Proliferation*
  • Cells, Cultured
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism*
  • Focal Adhesions / genetics
  • Focal Adhesions / metabolism*
  • Humans
  • Mechanotransduction, Cellular*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Transcription Factors
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Focal Adhesion Kinase 1
  • PTK2 protein, human