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KSR stimulates Raf-1 activity in a kinase-independent manner
Open accessAbstract
Kinase suppressor of Ras (KSR) is an evolutionarily conserved component of Ras-dependent signaling pathways. Here, we find that murine KSR (mKSR1) translocates from the cytoplasm to the plasma membrane in the presence of activated Ras. At the membrane, mKSR1 modulates Ras signaling by enhancing Raf-1 activity in a kinase-independent manner. The activation of Raf-1 is mediated by the mKSR1 cysteine-rich CA3 domain and involves a detergent labile cofactor that is not ceramide. These findings reveal another point of regulation for Ras-mediated signal transduction and further define a noncatalytic role for mKSR1 in the multistep process of Raf-1 activation.
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Phosphatidylinositol-3-OH kinase direct target of Ras
Rodriguez-Viciana, P., Warne, P. H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M. J., Waterfield, M. D., & Downward, J. (1994) · Nature · doi:10.1038/370527a0 · Cited by 1,954
Taxonomy and function of C1 protein kinase C homology domains
Hurley, J. H., Newton, A. C., Parker, P. J., Blumberg, P. M., & Nishizuka, Y. (1997) · Protein Science · doi:10.1002/pro.5560060228 · Cited by 362
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Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions
Kölch, W. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3510289 · Cited by 1,441
The MEK/ERK cascade: From signaling specificity to diverse functions
Shaul, Y. D., & Seger, R. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.10.005 · Cited by 940
Chen, Z., Gibson, T. B., Robinson, F., Silvestro, L., Pearson, G., Xu, B.-E., Wright, A., Vanderbilt, C., & Cobb, M. H. (2001) · Chemical Reviews · doi:10.1021/cr000241p · Cited by 788
Regulation of MAP Kinase Signaling Modules by Scaffold Proteins in Mammals
Morrison, D. K., & Davis, R. J. (2003) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.19.111401.091942 · Cited by 786
Self-citationTumor biomarkers for diagnosis, prognosis and targeted therapy
Zhou, Y., Tao, L., Qiu, J., Xu, J., Yang, X., Zhang, Y., Tian, X., Guan, X., Cen, X., & Zhao, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01823-2 · Cited by 720
Metadata
- Authors
- Michaud, N. R., Therrien, M., Cacace, A., Edsall, L. C., Spiegel, S., Rubin, G. M., & Morrison, D. K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1997-11-25
- Volume
- 94
- Issue
- 24
- Pages
- 12792-12796
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2074303585
- Cited by
- 166
- References
- 2
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- green
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- Michaud, N. R., Therrien, M., Cacace, A., Edsall, L. C., Spiegel, S., Rubin, G. M., & Morrison, D. K. (1997). KSR stimulates Raf-1 activity in a kinase-independent manner. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.94.24.12792
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