MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway

The Hippo pathway plays a central role in tissue homoeostasis, and its dysregulation contributes to tumorigenesis. Core components of the Hippo pathway include a kinase cascade of MST1/2 and LATS1/2 and the transcription co-activators YAP/TAZ. In response to stimulation, LATS1/2 phosphorylate and inhibit YAP/TAZ, the main effectors of the Hippo pathway. Accumulating evidence suggests that MST1/2 are not required for the regulation of YAP/TAZ. Here we show that deletion of LATS1/2 but not MST1/2 abolishes YAP/TAZ phosphorylation. We have identified MAP4K family members--Drosophila Happyhour homologues MAP4K1/2/3 and Misshapen homologues MAP4K4/6/7-as direct LATS1/2-activating kinases. Combined deletion of…

• DF
  Danmarks Frie Forskningsfond
• YM
  Yasuda Memorial Medical Foundation
• NI
  National Institutes of Health

  Awards: CA132809, CA196878, EY022611, DEO15964, T32 GM007752, GM007752
• UO
  University of California, San Diego

  Award: T32 GM007752
• JS
  Japan Society for the Promotion of Science