The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins
Open accessAbstract
How individual cells respond to mechanical forces is of considerable interest to biologists as force affects many aspects of cell behaviour. The application of force on integrins triggers cytoskeletal rearrangements and growth of the associated adhesion complex, resulting in increased cellular stiffness, also known as reinforcement. Although RhoA has been shown to play a role during reinforcement, the molecular mechanisms that regulate its activity are unknown. By combining biochemical and biophysical approaches, we identified two guanine nucleotide exchange factors (GEFs), LARG and GEF-H1, as key molecules that regulate the cellular adaptation to force. We show that stimulation of integrins with tensional force triggers activation of these two GEFs and their recruitment to adhesion complexes. Surprisingly, activation of LARG and GEF-H1 involves distinct signalling pathways. Our results reveal that LARG is activated by the Src family tyrosine kinase Fyn, whereas GEF-H1 catalytic activity is enhanced by ERK downstream of a signalling cascade that includes FAK and Ras.
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Cites
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Cited by
Calvo, F., Ege, N., Grande-Garcia, A., Hooper, S., Jenkins, R. P., Chaudhry, S. I., Harrington, K., Williamson, P., Moeendarbary, E., Charras, G., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2756 · Cited by 1,478
Integrins as biomechanical sensors of the microenvironment
Kechagia, J. Z., Ivaska, J., & Roca-Cusachs, P. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0134-2 · Cited by 1,311
Regulating Rho GTPases and their regulators
Hodge, R. G., & Ridley, A. J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.67 · Cited by 872
Lampi, M. C., & Reinhart-King, C. A. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aao0475 · Cited by 551
Rho GTPase signaling complexes in cell migration and invasion
Lawson, C. D., & Ridley, A. J. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201612069 · Cited by 539
Metadata
- Authors
- Guilluy, C., Swaminathan, V., Garcia-Mata, R., Timothy O’Brien, E., Superfine, R., & Burridge, K.
- Venue
- Nature Cell Biology
- Published
- 2011-05-15
- Volume
- 13
- Issue
- 6
- Pages
- 722-727
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2070439333
- Cited by
- 375
- References
- 39
- FWCI
- 12.80
- Type
- journal article
- Language
- en
- Open access
- green
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- Guilluy, C., Swaminathan, V., Garcia-Mata, R., Timothy O’Brien, E., Superfine, R., & Burridge, K. (2011). The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins. Nature Cell Biology. https://doi.org/10.1038/ncb2254
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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