The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Src-Mediated Phosphorylation of Focal Adhesion Kinase Couples Actin and Adhesion Dynamics to Survival Signaling
Open accessAbstract
Integrin-associated focal adhesions not only provide adhesive links between cellular actin and extracellular matrix but also are sites of signal transmission into the cell interior. Many cell responses signal through focal adhesion kinase (FAK), often by integrin-induced autophosphorylation of FAK or phosphorylation by Src family kinases. Here, we used an interfering FAK mutant (4-9F-FAK) to show that Src-dependent FAK phosphorylation is required for focal adhesion turnover and cell migration, by controlling assembly of a calpain 2/FAK/Src/p42ERK complex, calpain activation, and proteolysis of FAK. Expression of 4-9F-FAK in FAK-deficient fibroblasts also disrupts F-actin assembly associated with normal adhesion and spreading. In addition, we found that FAK's ability to regulate both assembly and disassembly of the actin and adhesion networks may be linked to regulation of the protease calpain. Surprisingly, we also found that the same interfering 4-9F-FAK mutant protein causes apoptosis of serum-deprived, transformed cells and suppresses anchorage-independent growth. These data show that Src-mediated phosphorylation of FAK acts as a pivotal regulator of both actin and adhesion dynamics and survival signaling, which, in turn, control apparently distinct processes such as cell migration and anchorage-independent growth. This also highlights that dynamic regulation of actin and adhesions (which include the integrin matrix receptors) is critical to signaling output and biological responses.
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Cites
Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase
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Regulation of Cell Migration by the Calcium-dependent Protease Calpain
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Elevated c-Src tyrosine kinase activity in premalignant epithelia of ulcerative colitis.
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Site-Specific Differences in pp60c-src Activity in Human Colorectal Metastases
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Focal adhesion kinase: in command and control of cell motility.
Mitra, S. K., Hanson, D. A., & Schlaepfer, D. D. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1549 · Cited by 2,335
Mechanisms and regulation of endothelial VEGF receptor signalling
Simons, M., Gordon, E., & Claesson-Welsh, L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.87 · Cited by 1,498
An integrin αvβ3–c-Src oncogenic unit promotes anchorage-independence and tumor progression
Desgrosellier, J. S., Barnes, L. A., Shields, D. J., Huang, M., Lau, S. K., Prévost, N., Tarin, D., Shattil, S. J., & Cheresh, D. A. (2009) · Nature Medicine · doi:10.1038/nm.2009 · Cited by 293
Schlessinger, K., & Levy, D. E. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0317 · Cited by 112
Cigarette Smoke Induces Cellular Senescence via Werner's Syndrome Protein Down-regulation
Nyunoya, T., Monick, M. M., Klingelhutz, A. L., Glaser, H., Cagley, J. R., Brown, C. O., Matsumoto, E., Aykin-Burns, N., Spitz, D. R., Oshima, J., et al. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200802-320oc · Cited by 79
Metadata
- Authors
- Westhoff, M. A., Serrels, B., Fincham, V. J., Frame, M. C., & Carragher, N. O.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-09-01
- Volume
- 24
- Issue
- 18
- Pages
- 8113-8133
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2100996687
- Cited by
- 263
- References
- 7
- FWCI
- 6.67
- Type
- journal article
- Language
- en
- Open access
- green
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- Westhoff, M. A., Serrels, B., Fincham, V. J., Frame, M. C., & Carragher, N. O. (2004). Src-Mediated Phosphorylation of Focal Adhesion Kinase Couples Actin and Adhesion Dynamics to Survival Signaling. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.24.18.8113-8133.2004
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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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