Activation of the yeast Hippo pathway by phosphorylation-dependent assembly of signaling complexes

Science. 2013 May 17;340(6134):871-5. doi: 10.1126/science.1235822. Epub 2013 Apr 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anaphase
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • Deoxyribonucleases / chemistry
  • Deoxyribonucleases / metabolism*
  • Enzyme Activation
  • GTP-Binding Proteins / metabolism*
  • Mitosis*
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Conformation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • tRNA Methyltransferases / chemistry
  • tRNA Methyltransferases / metabolism*

Substances

  • CDC15 protein
  • Cell Cycle Proteins
  • MOB1 protein, S cerevisiae
  • Phosphoproteins
  • Saccharomyces cerevisiae Proteins
  • tRNA Methyltransferases
  • DBF2 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • Deoxyribonucleases
  • TRM2 protein, S cerevisiae
  • GTP-Binding Proteins

Associated data

  • PDB/4JIZ