FAK controls the mechanical activation of YAP, a transcriptional regulator required for durotaxis
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. FASEB J. 32, 1099–1107 (2018). www.fasebj.org
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FAK activates and accumulates YAP in cell nucleus through regulation of the MOB1/LATS1/2 complex.
“FAK is known to activate and accumulate YAP in cell nucleus through its regulation of the MOB1/LATS1/2 complex, which is an upstream biomarker of YAP signaling[ 31, 32 ]”
From Focal Adhesion Kinase (FAK) Inhibition Synergizes with KRAS G12C Inhibitors in Treating Cancer through the Regulation of the FAK–YAP Signaling (2021) · cites this paper as [32]
FAK positively regulates YAP activity through tyrosine phosphorylation of the YAP upstream modulator MOB1, then dissociating the MOB1/LATS complex.
“On the other hand, FAK was reported to positively regulate YAP activity through tyrosine phosphorylation of the YAP upstream modulator MOB1, then dissociating the MOB1/LATS complex.[ 31, 32 ]”
From Focal Adhesion Kinase (FAK) Inhibition Synergizes with KRAS G12C Inhibitors in Treating Cancer through the Regulation of the FAK–YAP Signaling (2021) · cites this paper as [32]
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References 41 · Cited by 175
- Authors
- Lachowski, D., Cortes, E., Robinson, B., Rice, A., Rombouts, K., & Del Río Hernández, A. E.
- Affiliations
- Imperial College London (GB)
- Cellular and Molecular Biomechanics Laboratory Department of Bioengineering Imperial College London London United Kingdom
- The Royal Free Hospital (GB)
- Corresponding author
- Rombouts, Krista
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2018-01-03
- Volume
- 32
- Issue
- 2
- Pages
- 1099-1107
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2766216977
- Cited by
- 175
- References
- 41
- Citations by year
- 2026: 16 · 2025: 16 · 2024: 26 · 2023: 20 · 2022: 24 · 2021: 24 · 2020: 21 · 2019: 14 · 2018: 14
- FWCI
- 7.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- focal adhesion kinase, YAP, durotaxis, cell mechanosensing, mechanotransduction, nuclear translocation, cell mechanics, focal adhesions, cell migration
- MeSH terms
- YAP-Signaling Proteins, Cell Movement, Cells, Cultured, Humans, Phosphoproteins, Transcription Factors, Apoptosis, Focal Adhesions, Mechanotransduction, Cellular, Adaptor Proteins, Signal Transducing, Cell Proliferation, Focal Adhesion Kinase 1
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