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FAK integrates growth-factor and integrin signals to promote cell migration
Open accessAbstract
Here we show that cells lacking focal adhesion kinase (FAK) are refractory to motility signals from platelet-derived and epidermal growth factors (PDGF and EGF respectively), and that stable re-expression of FAK rescues these defects. FAK associates with activated PDGF- and EGF-receptor (PDGFR and EGFR) signalling complexes, and expression of the band-4.1-like domain at the FAK amino terminus is sufficient to mediate an interaction with activated EGFR. However, efficient EGF-stimulated cell migration also requires FAK to be targeted, by its carboxy-terminal domain, to sites of integrin-receptor clustering. Although the kinase activity of FAK is not needed to promote PDGF- or EGF-stimulated cell motility, kinase-inactive FAK is transphosphorylated at the indispensable Src-kinase-binding site, FAK Y397, after EGF stimulation of cells. Our results establish that FAK is an important receptor-proximal link between growth-factor-receptor and integrin signalling pathways.
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Giancotti, F. G., & Ruoslahti, E. (1999) · Science · doi:10.1126/science.285.5430.1028 · Cited by 3,869
Cited by
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Mitra, S. K., Hanson, D. A., & Schlaepfer, D. D. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1549 · Cited by 2,335
Self-citationFrisch, S. M., & Screaton, R. A. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00251-9 · Cited by 1,249
Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer
Wu, F., Yang, J., Liu, J., Wang, Y., Mu, J., Zeng, Q., Deng, S., & Zhou, H. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00641-0 · Cited by 773
White, D. E., Kurpios, N. A., Zuo, D., Hassell, J. A., Blaess, S., Mueller, U., & Muller, W. J. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.025 · Cited by 413
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Metadata
- Authors
- Sieg, D. J., Hauck, C. R., Ilic, D., Klingbeil, C. K., Schaefer, E., Damsky, C. H., & Schlaepfer, D. D.
- Venue
- Nature Cell Biology
- Published
- 2000-03-27
- Volume
- 2
- Issue
- 5
- Pages
- 249-256
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W1577573926
- Cited by
- 1,240
- References
- 1
- FWCI
- 31.51
- Type
- journal article
- Language
- en
- Open access
- green
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- Sieg, D. J., Hauck, C. R., Ilic, D., Klingbeil, C. K., Schaefer, E., Damsky, C. H., & Schlaepfer, D. D. (2000). FAK integrates growth-factor and integrin signals to promote cell migration. Nature Cell Biology. https://doi.org/10.1038/35010517
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
