Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes
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-s...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Association for the Advancement of Science (AAAS)
2014
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| Online Access: | http://hdl.handle.net/1721.1/85195 https://orcid.org/0000-0002-9547-3251 https://orcid.org/0000-0001-9837-0314 |
| _version_ | 1826198475206819840 |
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| author | 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 Yaffe, Michael B Amon, Angelika B |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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 Yaffe, Michael B Amon, Angelika B |
| author_sort | Lim, Daniel Cham-Chin |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:05:32Z |
| format | Article |
| id | mit-1721.1/85195 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:05:32Z |
| publishDate | 2014 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/851952022-09-27T17:04:29Z Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes 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 Yaffe, Michael B Amon, Angelika B Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Rock, Jeremy M. Lim, Daniel Cham-Chin Yaffe, Michael B. Amon, Angelika B. 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. National Institutes of Health (U.S.) (GM056800) National Institutes of Health (U.S.) (CA112967) National Institutes of Health (U.S.) (ES015339) National Science Foundation (U.S.) (Predoctoral Fellowship) 2014-02-28T18:07:40Z 2014-02-28T18:07:40Z 2013-04 2013-01 Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 http://hdl.handle.net/1721.1/85195 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. https://orcid.org/0000-0002-9547-3251 https://orcid.org/0000-0001-9837-0314 en_US http://dx.doi.org/10.1126/science.1235822 Science Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | 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 Yaffe, Michael B Amon, Angelika B Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes |
| title | Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes |
| title_full | Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes |
| title_fullStr | Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes |
| title_full_unstemmed | Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes |
| title_short | Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes |
| title_sort | activation of the yeast hippo pathway by phosphorylation dependent assembly of signaling complexes |
| url | http://hdl.handle.net/1721.1/85195 https://orcid.org/0000-0002-9547-3251 https://orcid.org/0000-0001-9837-0314 |
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