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Focal adhesion kinase (pp125FAK) cleavage and regulation by calpain
Open accessAbstract
Focal adhesion kinase (125 kDa form; pp125FAK) is a widely expressed non-receptor tyrosine kinase that is implicated in integrin-mediated signal transduction. We have identified a novel means of pp125FAK regulation in human platelets, in which this kinase undergoes sequential proteolytic modification from the native 125 kDa form to 90, 45 and 40 kDa fragments in thrombin-, collagen- and ionophore A23187-stimulated platelets. The proteolysis of pp125FAK was prevented by pretreating platelets with the calpain inhibitors calpeptin or calpain inhibitor-1, and was reproduced in vitro by incubating immunoprecipitated pp125FAK with purified calpain. Proteolysis of pp125FAK resulted in a dramatic reduction in its autokinase activity and led to its dissociation from the cytoskeletal fraction of platelets. These studies define a novel signal-terminating role for calpain, wherein proteolytic modification of pp125FAK attenuates its autokinase activity and induces its subcellular relocation within the cell.
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Cites
Signal transduction from the extracellular matrix.
Juliano, R. L., & Haskill, S. (1993) · The Journal of cell biology · doi:10.1083/jcb.120.3.577 · Cited by 1,683
Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase
Schlaepfer, D. D., Hanks, S. K., Hunter, T., & Geer, P. V. D. (1994) · Nature · doi:10.1038/372786a0 · Cited by 1,595
Cited by
Calpain and caspase: can you tell the difference?
Wang, K. K. W. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01479-4 · Cited by 912
Regulation of Cell Migration by the Calcium-dependent Protease Calpain
Huttenlocher, A., Palecek, S. P., Lu, Q., Zhang, W., Mellgren, R. L., Lauffenburger, D. A., Ginsberg, M. H., & Horwitz, A. F. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.52.32719 · Cited by 390
Focal adhesion and actin dynamics: a place where kinases and proteases meet to promote invasion
Carragher, N. O., & Frame, M. C. (2004) · Trends in Cell Biology · doi:10.1016/j.tcb.2004.03.011 · Cited by 373
Glading, A., Bodnar, R. J., Reynolds, I. J., Shiraha, H., Satish, L., Potter, D. A., Blair, H. C., & Wells, A. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.6.2499-2512.2004 · Cited by 271
Westhoff, M. A., Serrels, B., Fincham, V. J., Frame, M. C., & Carragher, N. O. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.18.8113-8133.2004 · Cited by 263
Metadata
- Authors
- COORAY, P., YUAN, Y., SCHOENWAELDER, S. M., MITCHELL, C. A., SALEM, H. H., & JACKSON, S. P.
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1996-08-15
- Volume
- 318
- Issue
- 1
- Pages
- 41-47
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- OpenAlex
- W2162164344
- Cited by
- 162
- References
- 2
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Focal adhesion kinase (pp125FAK) cleavage and regulation by calpain. https://app.cochat.ai/papers/10.1042/bj3180041
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- COORAY, P., YUAN, Y., SCHOENWAELDER, S. M., MITCHELL, C. A., SALEM, H. H., & JACKSON, S. P. (1996). Focal adhesion kinase (pp125FAK) cleavage and regulation by calpain. Biochemical Journal. https://doi.org/10.1042/bj3180041
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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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