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Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes

DOI: 10.1126/science.1235822 DOI Help
PMID: 23579499 PMID Help

Authors: J. M. Rock (Massachusetts Institute of Technology) , D. Lim (Massachusetts Institute of Technology) , L. Stach (MRC National Institute for Medical Research) , R. Ogrodowicz (MRC, National Institute for Medical Research) , J. M. Keck (University of Colorado) , M. H. Jones (University of Colorado) , C. C. L. Wong (Scripps Research Institute) , J. R. Yates (Scripps Research Institute) , M. Winey (University of Colorado) , Stephen Smerdon (MRC National Institute for Medical Research) , M. B. Yaffe (Massachusetts Institute of Technology) , A. Amon (Massachusetts Institute of Technology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science

State: Published (Approved)
Published: April 2013
Diamond Proposal Number(s): 7707

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.

Journal Keywords: Cell; Deoxyribonucleases; Enzyme; GTP-Binding; Mitosis; Phosphoproteins; Phosphorylation; Protein; Protein-Serine-Threonine; Saccharomyces; Saccharomyces; Signal; tRNA Methyltransferases

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography

Added On: 12/04/2013 11:28

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