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

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

Research output: Contribution to journalArticle

59 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)871-875
Number of pages5
JournalScience
Volume340
Issue number6134
DOIs
StatePublished - May 17 2013
Externally publishedYes

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Phosphotransferases
Yeasts
Phosphorylation
Phosphoserine
Saccharomycetales
G1 Phase
Threonine
Mitosis
Signal Transduction
Decision Making
Cell Cycle
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

Rock, J. M., Lim, D., Stach, L., Ogrodowicz, R. W., Keck, J. M., Jones, M. H., ... Amon, A. (2013). Activation of the yeast Hippo pathway by phosphorylation-dependent assembly of signaling complexes. Science, 340(6134), 871-875. https://doi.org/10.1126/science.1235822

Activation of the yeast Hippo pathway by phosphorylation-dependent assembly of signaling complexes. / Rock, Jeremy M.; Lim, Daniel; Stach, Lasse; Ogrodowicz, Roksana W.; Keck, Jamie M.; Jones, Michele H.; Wong, Catherine C.L.; Yates, John R.; Winey, Mark; Smerdon, Stephen J.; Yaffe, Michael B.; Amon, Angelika.

In: Science, Vol. 340, No. 6134, 17.05.2013, p. 871-875.

Research output: Contribution to journalArticle

Rock, JM, Lim, D, Stach, L, Ogrodowicz, RW, Keck, JM, Jones, MH, Wong, CCL, Yates, JR, Winey, M, Smerdon, SJ, Yaffe, MB & Amon, A 2013, 'Activation of the yeast Hippo pathway by phosphorylation-dependent assembly of signaling complexes', Science, vol. 340, no. 6134, pp. 871-875. https://doi.org/10.1126/science.1235822
Rock JM, Lim D, Stach L, Ogrodowicz RW, Keck JM, Jones MH et al. Activation of the yeast Hippo pathway by phosphorylation-dependent assembly of signaling complexes. Science. 2013 May 17;340(6134):871-875. https://doi.org/10.1126/science.1235822
Rock, Jeremy M. ; Lim, Daniel ; Stach, Lasse ; Ogrodowicz, Roksana W. ; Keck, Jamie M. ; Jones, Michele H. ; Wong, Catherine C.L. ; Yates, John R. ; Winey, Mark ; Smerdon, Stephen J. ; Yaffe, Michael B. ; Amon, Angelika. / Activation of the yeast Hippo pathway by phosphorylation-dependent assembly of signaling complexes. In: Science. 2013 ; Vol. 340, No. 6134. pp. 871-875.
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