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Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors
Open accessAbstract
The Ras-related GTPase Rap1 stimulates integrin-mediated adhesion and spreading in various mammalian cell types. Here, we demonstrate that Rap1 regulates cell spreading by localizing guanine nucleotide exchange factors (GEFs) that act via the Rho family GTPase Rac1. Rap1a activates Rac1 and requires Rac1 to enhance spreading, whereas Rac1 induces spreading independently of Rap1. Active Rap1a binds to a subset of Rac GEFs, including VAV2 and Tiam1 but not others such as SWAP-70 or COOL-1. Overexpressed VAV2 and Tiam1 specifically require Rap1 to promote spreading, even though Rac1 is activated independently of Rap1. Rap1 is necessary for the accumulation of VAV2 in membrane protrusions at the cell periphery. In addition, if VAV2 is artificially localized to the cell edge with the subcellular targeting domain of Rap1a, it increases cell spreading independently of Rap1. These results lead us to propose that Rap1 promotes cell spreading by localizing a subset of Rac GEFs to sites of active lamellipodia extension.
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Hynes (2002) · doi:10.1016/s0092-8674(02)00971-6 · Cited by 8,606
Castro, A. F., Rebhun, J. F., Clark, G. J., & Quilliam, L. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c300226200 · Cited by 381
Self-citation
Cited by
GEFs and GAPs: Critical Elements in the Control of Small G Proteins
Bos, J. L., Rehmann, H., & Wittinghofer, A. (2007) · Cell · doi:10.1016/j.cell.2007.05.018 · Cited by 1,903
Genetic and cell biological analysis of integrin outside-in signaling
Legate, K. R., Wickström, S. A., & Fässler, R. (2009) · Genes & Development · doi:10.1101/gad.1758709 · Cited by 802
Epac proteins: multi-purpose cAMP targets
Bos, J. L. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.10.002 · Cited by 532
Intracellular signalling controlling integrin activation in lymphocytes
Kinashi, T. (2005) · Nature Reviews Immunology · doi:10.1038/nri1646 · Cited by 477
Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP
Shibasaki, T., Takahashi, H., Miki, T., Sunaga, Y., Matsumura, K., Yamanaka, M., Zhang, C., Tamamoto, A., Satoh, T., Miyazaki, J.-I., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707054104 · Cited by 425
Metadata
- Authors
- Arthur, W. T., Quilliam, L. A., & Cooper, J. A.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2004-10-11
- Volume
- 167
- Issue
- 1
- Pages
- 111-122
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2132793070
- Cited by
- 253
- References
- 2
- FWCI
- 6.34
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Arthur, W. T., Quilliam, L. A., & Cooper, J. A. (2004). Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200404068
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