학술논문

Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes
Document Type
Academic Journal
Source
Science. May 17, 2013 340(6134):871-875
Subject
Language
English
ISSN
0036-8075
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-Mobl bound through a phosphoserine-threonine binding domain, in order to be activated by Cdcl5. This mechanism of pathway activation has implications for signal transmission through other kinase cascades and might represent a general principle in scaffold-assisted signaling.