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Rewiring MAP Kinase Pathways Using Alternative Scaffold Assembly Mechanisms
Abstract
How scaffold proteins control information flow in signaling pathways is poorly understood: Do they simply tether components, or do they precisely orient and activate them? We found that the yeast mitogen-activated protein (MAP) kinase scaffold Ste5 is tolerant to major stereochemical perturbations; heterologous protein interactions could functionally replace native kinase recruitment interactions, indicating that simple tethering is largely sufficient for scaffold-mediated signaling. Moreover, by engineering a scaffold that tethers a unique kinase set, we could create a synthetic MAP kinase pathway with non-natural input-output properties. These findings demonstrate that scaffolds are highly flexible organizing factors that can facilitate pathway evolution and engineering.
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Cites
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Choi, K.-W., & Benzer, S. (1994) · Cell · doi:10.1016/0092-8674(94)90579-7 · Cited by 339
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Ubersax, J. A., & Ferrell Jr, J. E. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2203 · Cited by 1,451
Synthetic biology: new engineering rules for an emerging discipline
Andrianantoandro, E., Basu, S., Karig, D. K., & Weiss, R. (2006) · Molecular Systems Biology · doi:10.1038/msb4100073 · Cited by 1,081
A brief history of synthetic biology
Cameron, D. E., Bashor, C. J., & Collins, J. J. (2014) · Nature Reviews Microbiology · doi:10.1038/nrmicro3239 · Cited by 933
Benner, S. A., & Sismour, A. M. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1637 · Cited by 834
Engineering drought tolerance in plants: discovering and tailoring genes to unlock the future
Umezawa, T., Fujita, M., Fujita, Y., Yamaguchi-Shinozaki, K., & Shinozaki, K. (2006) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2006.02.002 · Cited by 802
Metadata
- Authors
- Park, S.-H., Zarrinpar, A., & Lim, W. A.
- Venue
- Science
- Published
- 2003-02-14
- Volume
- 299
- Issue
- 5609
- Pages
- 1061-1064
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2063354556
- Cited by
- 355
- References
- 1
- FWCI
- 11.15
- Type
- journal article
- Language
- en
- Open access
- closed
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