Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes
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Author(s)
Lim, Daniel Cham-Chin
Stach, Lasse
Ogrodowicz, Roksana W.
Keck, Jamie M.
Jones, Michele H.
Wong, Catherine C. L.
Yates, John R., III
Winey, Mark
Smerdon, Stephen J.
Rock, Jeremy Michael
Date Issued
April 2013
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Rock, J. M., D. Lim, L. Stach, R. W. Ogrodowicz, J. M. Keck, M. H. Jones, C. C. L. Wong, et al. “Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes.” Science 340, no. 6134 (May 17, 2013): 871–875.
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Author's final manuscript
Abstract
Scaffold-assisted signaling cascades guide cellular decision-making. In budding yeast, one such signal transduction pathway called the mitotic exit network (MEN) governs the transition from mitosis to the G1 phase of the cell cycle. The MEN is conserved and in metazoans is known as the Hippo tumor-suppressor pathway. We found that signaling through the MEN kinase cascade was mediated by an unusual two-step process. The MEN kinase Cdc15 first phosphorylated the scaffold Nud1. This created a phospho-docking site on Nud1, to which the effector kinase complex Dbf2-Mob1 bound through a phosphoserine-threonine binding domain, in order to be activated by Cdc15. This mechanism of pathway activation has implications for signal transmission through other kinase cascades and might represent a general principle in scaffold-assisted signaling.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1126/science.1235822
