Structural basis for Mob1-dependent activation of the core Mst–Lats kinase cascade in Hippo signaling

Lisheng Ni, Yonggang Zheng, Mayuko Hara, Duojia Pan, Xuelian Luo

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


The Mst–Lats kinase cascade is central to the Hippo tumor-suppressive pathway that controls organ size and tissue homeostasis. The adaptor protein Mob1 promotes Lats activation by Mst, but the mechanism remains unknown. Here, we show that human Mob1 binds to autophosphorylated docking motifs in active Mst2. This binding enables Mob1 phosphorylation by Mst2. Phosphorylated Mob1 undergoes conformational activation and binds to Lats1. We determine the crystal structures of phospho-Mst2–Mob1 and phospho-Mob1–Lats1 complexes, revealing the structural basis of both phosphorylation-dependent binding events. Further biochemical and functional analyses demonstrate that Mob1 mediates Lats1 activation through dynamic scaffolding and allosteric mechanisms. Thus, Mob1 acts as a phosphorylation-regulated coupler of kinase activation by virtue of its ability to engage multiple ligands. We propose that stepwise, phosphorylation-triggered docking interactions of nonkinase elements enhance the specificity and robustness of kinase signaling cascades.

Original languageEnglish (US)
Pages (from-to)1416-1431
Number of pages16
JournalGenes & development
Issue number13
StatePublished - Jul 1 2015


  • Autoinhibition
  • Lats1
  • Mob1
  • Mst2
  • NMR
  • Phosphorylation
  • X-ray crystallography

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


Dive into the research topics of 'Structural basis for Mob1-dependent activation of the core Mst–Lats kinase cascade in Hippo signaling'. Together they form a unique fingerprint.

Cite this