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Vinculin modulation of paxillin–FAK interactions regulates ERK to control survival and motility
Open accessAbstract
Cells lacking vinculin are highly metastatic and motile. The reasons for this finding have remained unclear. Both enhanced survival and motility are critical to metastasis. Here, we show that vinculin null (vin−/−) cells and cells expressing a vinculin Y822F mutant have increased survival due to up-regulated activity of extracellular signal–regulated kinase (ERK). This increase is shown to result from vinculin's modulation of paxillin–FAK interactions. A vinculin fragment (amino acids 811–1066) containing the paxillin binding site restored apoptosis and suppressed ERK activity in vin−/− cells. Both vinY822F and vin−/− cells exhibit increased interaction between paxillin and focal adhesion kinase (FAK) and increased paxillin and FAK phosphorylation. Transfection with paxillin Y31FY118F dominant-negative mutant in these cells inhibits ERK activation and restores apoptosis. The enhanced motility of vin−/− and vinY822F cells is also shown to be due to a similar mechanism. Thus, vinculin regulates survival and motility via ERK by controlling the accessibility of paxillin for FAK interaction.
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Cites
Role of cell shape in growth control
Folkman, J., & Moscona, A. (1978) · Nature · doi:10.1038/273345a0 · Cited by 2,422
Cited by
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
Effect of WAVE2 Phosphorylation on Activation of the Arp2/3 Complex
Nakanishi, O., Suetsugu, S., Yamazaki, D., & Takenawa, T. (2006) · Journal of Biochemistry · doi:10.1093/jb/mvm034 · Cited by 50
Metadata
- Authors
- Subauste, M. C., Pertz, O., Adamson, E. D., Turner, C. E., Junger, S., & Hahn, K. M.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2004-05-10
- Volume
- 165
- Issue
- 3
- Pages
- 371-381
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2100491916
- Cited by
- 272
- References
- 1
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- green
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- Subauste, M. C., Pertz, O., Adamson, E. D., Turner, C. E., Junger, S., & Hahn, K. M. (2004). Vinculin modulation of paxillin–FAK interactions regulates ERK to control survival and motility. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200308011
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