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

Overview

Journal Science

Specialty Science

Date 2013 Apr 13

PMID 23579499

Citations 64

Authors

Jeremy M Rock

Daniel Lim

Lasse Stach

Roksana W Ogrodowicz

Jamie M Keck

Michele H Jones

Catherine C L Wong

John R Yates 3rd

Mark Winey

Stephen J Smerdon

Michael B Yaffe

Angelika Amon

Affiliations

Soon will be listed here.

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.

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