Title | Activation of the yeast Hippo pathway by phosphorylation-dependent assembly of signaling complexes. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Rock, JM, Lim, D, Stach, L, Ogrodowicz, RW, Keck, JM, Jones, MH, Wong, CCL, Yates, JR, Winey, M, Smerdon, SJ, Yaffe, MB, Amon, A |
Journal | Science |
Volume | 340 |
Issue | 6134 |
Pagination | 871-5 |
Date Published | 2013 May 17 |
ISSN | 1095-9203 |
Keywords | Anaphase, Cell Cycle Proteins, Deoxyribonucleases, Enzyme Activation, GTP-Binding Proteins, Mitosis, Phosphoproteins, Phosphorylation, Protein Conformation, Protein-Serine-Threonine Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, tRNA Methyltransferases |
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. |
DOI | 10.1126/science.1235822 |
Alternate Journal | Science |
PubMed ID | 23579499 |
Grant List | CA112967 / CA / NCI NIH HHS / United States ES015339 / ES / NIEHS NIH HHS / United States F32 GM086038 / GM / NIGMS NIH HHS / United States GM056800 / GM / NIGMS NIH HHS / United States GM51312 / GM / NIGMS NIH HHS / United States P41 RR011823 / RR / NCRR NIH HHS / United States R01 GM051312 / GM / NIGMS NIH HHS / United States U117584228 / / Medical Research Council / United Kingdom / / Howard Hughes Medical Institute / United States |