Meng, Z., Moroishi, T., Mottier-Pavie, V., Plouffe, S.W., Hansen, C.G., Hong, A.W., Park, H.W., Mo, J.S., Lu, W., Lu, S., Flores, F., Yu, F.X., Halder, G., Guan, K.L. (2015). MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway.  Nat. Commun. 6(): 8357.

FBrf0229740

Research paper

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.

PMC4600732 (PMC) (EuropePMC)