The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Localized Ras signaling at the leading edge regulates PI3K, cell polarity, and directional cell movement
Open accessAbstract
During chemotaxis, receptors and heterotrimeric G-protein subunits are distributed and activated almost uniformly along the cell membrane, whereas PI(3,4,5)P3, the product of phosphatidylinositol 3-kinase (PI3K), accumulates locally at the leading edge. The key intermediate event that creates this strong PI(3,4,5)P3 asymmetry remains unclear. Here, we show that Ras is rapidly and transiently activated in response to chemoattractant stimulation and regulates PI3K activity. Ras activation occurs at the leading edge of chemotaxing cells, and this local activation is independent of the F-actin cytoskeleton, whereas PI3K localization is dependent on F-actin polymerization. Inhibition of Ras results in severe defects in directional movement, indicating that Ras is an upstream component of the cell's compass. These results support a mechanism by which localized Ras activation mediates leading edge formation through activation of basal PI3K present on the plasma membrane and other Ras effectors required for chemotaxis. A feedback loop, mediated through localized F-actin polymerization, recruits cytosolic PI3K to the leading edge to amplify the signal.
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Cites
Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J. L., Bonenfant, D., Oppliger, W., Jenoe, P., & Hall, M. N. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00636-6 · Cited by 1,886
Parent, C. A., & Devreotes, P. N. (1999) · Science · doi:10.1126/science.284.5415.765 · Cited by 890
Polarization of Chemoattractant Receptor Signaling During Neutrophil Chemotaxis
Servant, G., Weiner, O. D., Herzmark, P., Balla, T., Sedat, J. W., & Bourne, H. R. (2000) · Science · doi:10.1126/science.287.5455.1037 · Cited by 877
Ras proteins: different signals from different locations
Hancock, J. F. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1105 · Cited by 756
Spatial and Temporal Regulation of 3-Phosphoinositides by PI 3-Kinase and PTEN Mediates Chemotaxis
Funamoto, S., Meili, R., Lee, S., Parry, L., & Firtel, R. A. (2002) · Cell · doi:10.1016/s0092-8674(02)00755-9 · Cited by 751
Self-citationDivergent Signals and Cytoskeletal Assemblies Regulate Self-Organizing Polarity in Neutrophils
Xu, J., Wang, F., Van Keymeulen, A., Herzmark, P., Straight, A., Kelly, K., Takuwa, Y., Sugimoto, N., Mitchison, T., & Bourne, H. R. (2003) · Cell · doi:10.1016/s0092-8674(03)00555-5 · Cited by 685
Tumor Suppressor PTEN Mediates Sensing of Chemoattractant Gradients
Iijima, M., & Devreotes, P. (2002) · Cell · doi:10.1016/s0092-8674(02)00745-6 · Cited by 677
G Protein Signaling Events Are Activated at the Leading Edge of Chemotactic Cells
Parent, C. A., Blacklock, B. J., Froehlich, W. M., Murphy, D. B., & Devreotes, P. N. (1998) · Cell · doi:10.1016/s0092-8674(00)81784-5 · Cited by 617
Crystal Structure and Functional Analysis of Ras Binding to Its Effector Phosphoinositide 3-Kinase γ
Pacold, M. E., Suire, S., Perisic, O., Lara-Gonzalez, S., Davis, C. T., Walker, E. H., Hawkins, P. T., Stephens, L., Eccleston, J. F., & Williams, R. L. (2000) · Cell · doi:10.1016/s0092-8674(00)00196-3 · Cited by 602
Ras signalling on the endoplasmic reticulum and the Golgi
Chiu, V. K., Bivona, T., Hach, A., Sajous, J. B., Silletti, J., Wiener, H., Johnson, R. L., Cox, A. D., & Philips, M. R. (2002) · Nature Cell Biology · doi:10.1038/ncb783 · Cited by 594 · cited 2×
“To determine the spatial-temporal kinetics of Ras activation in living cells, we used the GFP-tagged RBD of Raf1, which binds to and thus should monitor Ras-GTP levels and its localization in cells (Chiu et al., 2002; Hancock, 2003).”
Method
Cited by
Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
Balla, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00028.2012 · Cited by 1,638
Neuronal polarity: from extracellular signals to intracellular mechanisms.
Arimura, N., & Kaibuchi, K. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2056 · Cited by 655
Houk, A. R., Jilkine, A., Mejean, C. O., Boltyanskiy, R., Dufresne, E. R., Angenent, S. B., Altschuler, S. J., Wu, L. F., & Weiner, O. D. (2012) · Cell · doi:10.1016/j.cell.2011.10.050 · Cited by 565
Swaney, K. F., Huang, C.-H., & Devreotes, P. N. (2010) · Annual Review of Biophysics · doi:10.1146/annurev.biophys.093008.131228 · Cited by 494
Loovers, H. M., Postma, M., Keizer-Gunnink, I., Huang, Y. E., Devreotes, P. N., & van Haastert, P. J. M. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-09-0825 · Cited by 104
Metadata
- Authors
- Sasaki, A. T., Chun, C., Takeda, K., & Firtel, R. A.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2004-11-08
- Volume
- 167
- Issue
- 3
- Pages
- 505-518
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2146749791
- Cited by
- 366
- References
- 43
- FWCI
- 5.58
- Type
- journal article
- Language
- en
- Open access
- bronze
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