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

作者：Rock Jeremy M; Lim Daniel; Stach Lasse; Ogrodowicz Roksana W; Keck Jamie M; Jones Michele H; Wong Catherine C L; Yates John R III; Winey Mark; Smerdon Stephen J; Yaffe Michael B; Amon Angelika^*

来源：Science, 2013, 340(6134): 871-875.

DOI：10.1126/science.1235822

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 G(1) 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.

• 出版日期2013-5-17
• 单位河北医科大学