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

Author

Listed:
  • Zhipeng Meng

    (University of California San Diego)

  • Toshiro Moroishi

    (University of California San Diego)

  • Violaine Mottier-Pavie

    (Vlaams Instituut voor Biotechnologie Center for the Biology of Disease and Katholieke Universiteit Leuven Center for Human Genetics, University of Leuven)

  • Steven W. Plouffe

    (University of California San Diego)

  • Carsten G. Hansen

    (University of California San Diego)

  • Audrey W. Hong

    (University of California San Diego)

  • Hyun Woo Park

    (University of California San Diego)

  • Jung-Soon Mo

    (University of California San Diego)

  • Wenqi Lu

    (University of California San Diego)

  • Shicong Lu

    (University of California San Diego)

  • Fabian Flores

    (University of California San Diego)

  • Fa-Xing Yu

    (Children's Hospital and Institutes of Biomedical Sciences, Fudan University)

  • Georg Halder

    (Vlaams Instituut voor Biotechnologie Center for the Biology of Disease and Katholieke Universiteit Leuven Center for Human Genetics, University of Leuven)

  • Kun-Liang Guan

    (University of California San Diego)

Abstract

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 MAP4Ks and MST1/2, but neither alone, suppresses phosphorylation of LATS1/2 and YAP/TAZ in response to a wide range of signals. Our results demonstrate that MAP4Ks act in parallel to and are partially redundant with MST1/2 in the regulation of LATS1/2 and YAP/TAZ, and establish MAP4Ks as components of the expanded Hippo pathway.

Suggested Citation

  • Zhipeng Meng & Toshiro Moroishi & Violaine Mottier-Pavie & Steven W. Plouffe & Carsten G. Hansen & Audrey W. Hong & Hyun Woo Park & Jung-Soon Mo & Wenqi Lu & Shicong Lu & Fabian Flores & Fa-Xing Yu & , 2015. "MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway," Nature Communications, Nature, vol. 6(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9357
    DOI: 10.1038/ncomms9357
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    Cited by:

    1. Atanu Paul & Stefano Annunziato & Bo Lu & Tianliang Sun & Olivera Evrova & Lara Planas-Paz & Vanessa Orsini & Luigi M. Terracciano & Olga Charlat & Zinger Yang Loureiro & Lei Ji & Raffaella Zamponi & , 2022. "Cell adhesion molecule KIRREL1 is a feedback regulator of Hippo signaling recruiting SAV1 to cell-cell contact sites," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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