title: Activation of the yeast Hippo pathway by phosphorylation-dependent assembly of signaling complexes.
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.
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Rock
authors.forename: Daniel
authors.initials: D
authors.lastname: Lim
authors.forename: Lasse
authors.initials: L
authors.lastname: Stach
authors.forename: Roksana W
authors.initials: RW
authors.lastname: Ogrodowicz
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Keck
authors.forename: Michele H
authors.initials: MH
authors.lastname: Jones
authors.forename: Catherine C L
authors.initials: CC
authors.lastname: Wong
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Mark
authors.initials: M
authors.lastname: Winey
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Smerdon
authors.forename: Michael B
authors.initials: MB
authors.lastname: Yaffe
authors.forename: Angelika
authors.initials: A
authors.lastname: Amon
mesh_terms: D000705:Anaphase; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008938:Mitosis; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D012359:tRNA Methyltransferases / Q000737:chemistry / Q000378:metabolism*
chemical_list: C082279:CDC15 protein; D018797:Cell Cycle Proteins; C110689:MOB1 protein, S cerevisiae; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D012359:tRNA Methyltransferases; C085768:DBF2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D003851:Deoxyribonucleases; C077501:TRM2 protein, S cerevisiae; D019204:GTP-Binding Proteins