Report

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

+ See all authors and affiliations

Science  17 May 2013:
Vol. 340, Issue 6134, pp. 871-875
DOI: 10.1126/science.1235822

You are currently viewing the abstract.

View Full Text

Signal Scaffolds

Scaffolds in cellular signaling pathways are turning out to do way more than just hold proteins together in a complex. Kim et al. (p. 867, published online 11 April) showed the importance of the scaffold protein Axin as an active participant controlling the kinetics of activation of signaling through the pathways. Axin is part of two protein complexes that have opposing actions that may regulate the timing of signaling—either activating Wnt signaling, thus protecting β-catenin from destruction, or causing proteolytic destruction of β-catenin. Rock et al. (p. 871, published online 11 April) characterized the role of the scaffold protein Nud1 in the mitotic exit network and found that the kinase that produces the output from the signaling complex only interacts with a scaffold that is primed by its activator protein kinase, already bound to the scaffold and creating a docking site.

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.

View Full Text