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Kinase Suppressor of Ras (KSR) Is a Scaffold Which Facilitates Mitogen-Activated Protein Kinase Activation In Vivo
Open accessAbstract
While scaffold proteins are thought to be key components of signaling pathways, their exact function is unknown. By preassembling multiple components of signaling cascades, scaffolds are predicted to influence the efficiency and/or specificity of signaling events. Here we analyze a potential scaffold of the Ras/mitogen-activated protein kinase (MAPK) pathway, kinase suppressor of Ras (KSR), by generating KSR-deficient mice. KSR-deficient mice were grossly normal even though ERK kinase activation was attenuated to a degree sufficient to block T-cell activation and inhibit tumor development. Consistent with its role as a scaffold, high-molecular-weight complexes containing KSR, MEK, and ERK were lost in the absence of KSR. This demonstrates that KSR is a bona fide scaffold that is not required for but enhances signaling via the Ras/MAPK signaling pathway.
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Cites
Mitogen-Activated Protein Kinases: Specific Messages from Ubiquitous Messengers
Schaeffer, H. J., & Weber, M. J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.4.2435 · Cited by 1,600
Requirement of the JIP1 scaffold protein for stress-induced JNK activation
Whitmarsh, A. J., Kuan, C.-Y., Kennedy, N. J., Kelkar, N., Haydar, T. F., Mordes, J. P., Appel, M., Rossini, A. A., Jones, S. N., Flavell, R. A., et al. (2001) · Genes & Development · doi:10.1101/gad.922801 · Cited by 238
Cited by
MAP kinase signalling pathways in cancer
Dhillon, A. S., Hagan, S., Rath, O., & Kolch, W. (2007) · Oncogene · doi:10.1038/sj.onc.1210421 · Cited by 2,995
Regulation of RAF protein kinases in ERK signalling
Lavoie, H., & Therrien, M. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3979 · Cited by 702
RAF-MEK-ERK pathway in cancer evolution and treatment
Ullah, R., Yin, Q., Snell, A. H., & Wan, L. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.05.010 · Cited by 553
Ory, S., Zhou, M., Conrads, T. P., Veenstra, T. D., & Morrison, D. K. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00535-9 · Cited by 296
Self-citationSignaling dynamics of the KSR1 scaffold complex
McKay, M. M., Ritt, D. A., & Morrison, D. K. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901590106 · Cited by 163
Self-citationThe RhoGEF GEF-H1 is required for oncogenic RAS signaling via KSR-1
Cullis, J., Meiri, D., Sandi, M. J., Radulovich, N., Kent, O. A., Medrano, M., Mokady, D., Normand, J., Larose, J., Marcotte, R., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.01.025 · Cited by 100
The Therapeutic Landscape for KRAS-Mutated Colorectal Cancers
Tria, S. M., Burge, M. E., & Whitehall, V. L. J. (2023) · Cancers · doi:10.3390/cancers15082375 · Cited by 38
KSR induces RAS‐independent MAPK pathway activation and modulates the efficacy of KRAS inhibitors
Paniagua, G., Jacob, H. K. C., Brehey, O., García‐Alonso, S., Lechuga, C. G., Pons, T., Musteanu, M., Guerra, C., Drosten, M., & Barbacid, M. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13213 · Cited by 34
Metadata
- Authors
- Nguyen, A., Burack, W. R., Stock, J. L., Kortum, R., Chaika, O. V., Afkarian, M., Muller, W. J., Murphy, K. M., Morrison, D. K., Lewis, R. E., McNeish, J., & Shaw, A. S.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2002-05-01
- Volume
- 22
- Issue
- 9
- Pages
- 3035-3045
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2116669977
- Cited by
- 268
- References
- 2
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- green
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