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14-3-3 Proteins Are Required for Maintenance of Raf-1 Phosphorylation and Kinase Activity
Open accessAbstract
By binding to serine-phosphorylated proteins, 14-3-3 proteins function as effectors of serine phosphorylation. The exact mechanism of their action is, however, still largely unknown. Here we demonstrate a requirement for 14-3-3 for Raf-1 kinase activity and phosphorylation. Expression of dominant negative forms of 14-3-3 resulted in the loss of a critical Raf-1 phosphorylation, while overexpression of 14-3-3 resulted in enhanced phosphorylation of this site. 14-3-3 levels, therefore, regulate the stoichiometry of Raf-1 phosphorylation and its potential activity in the cell. Phosphorylation of Raf-1, however, was insufficient by itself for kinase activity. Removal of 14-3-3 from phosphorylated Raf abrogated kinase activity, whereas addition of 14-3-3 restored it. This supports a paradigm in which the effects of phosphorylation on serine as well as tyrosine residues are mediated by inducible protein-protein interactions.
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Citations
Cited by
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Wee, P., & Wang, Z. (2017) · Cancers · doi:10.3390/cancers9050052 · Cited by 2,027
14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport
Brunet, A., Kanai, F., Stehn, J., Xu, J., Sarbassova, D., Frangioni, J. V., Dalal, S. N., DeCaprio, J. A., Greenberg, M. E., & Yaffe, M. B. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200112059 · Cited by 561
14-3-3 proteins; bringing new definitions to scaffolding
Tzivion, G., Shen, Y. H., & Zhu, J. (2001) · Oncogene · doi:10.1038/sj.onc.1204777 · Cited by 300
Shumway, S. D., Li, Y., & Xiong, Y. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c200499200 · Cited by 74
Microtubule Integrity Regulates Pak Leading to Ras-independent Activation of Raf-1
Zang, M., Waelde, C. A., Xiang, X., Rana, A., Wen, R., & Luo, Z. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100152200 · Cited by 48
Metadata
- Authors
- Thorson, J. A., Yu, L. W. K., Hsu, A. L., Shih, N.-Y., Graves, P. R., Tanner, J. W., Allen, P. M., Piwnica-Worms, H., & Shaw, A. S.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1998-09-01
- Volume
- 18
- Issue
- 9
- Pages
- 5229-5238
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2155515046
- Cited by
- 220
- References
- 0
- FWCI
- 7.77
- Type
- journal article
- Language
- en
- Open access
- green
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- Thorson, J. A., Yu, L. W. K., Hsu, A. L., Shih, N.-Y., Graves, P. R., Tanner, J. W., Allen, P. M., Piwnica-Worms, H., & Shaw, A. S. (1998). 14-3-3 Proteins Are Required for Maintenance of Raf-1 Phosphorylation and Kinase Activity. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.18.9.5229
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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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