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

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, Georg Halder and Kun-Liang Guan ()
Additional contact information
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

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/ncomms9357 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9357

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9357

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().