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Activation of Rac and Cdc42 by Integrins Mediates Cell Spreading
Open accessAbstract
Adhesion to ECM is required for many cell functions including cytoskeletal organization, migration, and proliferation. We observed that when cells first adhere to extracellular matrix, they spread rapidly by extending filopodia-like projections and lamellipodia. These structures are similar to the Rac- and Cdc42-dependent structures observed in growth factor-stimulated cells. We therefore investigated the involvement of Rac and Cdc42 in adhesion and spreading on the ECM protein fibronectin. We found that integrin-dependent adhesion led to the rapid activation of p21-activated kinase, a downstream effector of Cdc42 and Rac, suggesting that integrins activate at least one of these GTPases. Dominant negative mutants of Rac and Cdc42 inhibit cell spreading in such a way as to suggest that integrins activate Cdc42, which leads to the subsequent activation of Rac; both GTPases then contribute to cell spreading. These results demonstrate that initial integrin-dependent activation of Rac and Cdc42 mediates cell spreading.
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Citations
Cited by
Giancotti, F. G., & Ruoslahti, E. (1999) · Science · doi:10.1126/science.285.5430.1028 · Cited by 3,869
Adhesion-Dependent Cell Mechanosensitivity
Bershadsky, A. D., Balaban, N. Q., & Geiger, B. (2003) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.19.111301.153011 · Cited by 874
Rho-family GTPases in cadherin-mediated cell — cell adhesion
Fukata, M., & Kaibuchi, K. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35103068 · Cited by 438
ERK-MAPK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility
Vial, E., Sahai, E., & Marshall, C. J. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00162-4 · Cited by 406
Humphries, J. D., Byron, A., Bass, M. D., Craig, S. E., Pinney, J. W., Knight, D., & Humphries, M. J. (2009) · Science Signaling · doi:10.1126/scisignal.2000396 · Cited by 404
Metadata
- Authors
- Price, L. S., Leng, J., Schwartz, M. A., & Bokoch, G. M.
- Venue
- Molecular Biology of the Cell
- Published
- 1998-07
- Volume
- 9
- Issue
- 7
- Pages
- 1863-1871
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- OpenAlex
- W2165525793
- Cited by
- 644
- References
- 0
- FWCI
- 11.48
- Type
- journal article
- Language
- en
- Open access
- green
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- Price, L. S., Leng, J., Schwartz, M. A., & Bokoch, G. M. (1998). Activation of Rac and Cdc42 by Integrins Mediates Cell Spreading. Molecular Biology of the Cell. https://doi.org/10.1091/mbc.9.7.1863
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