Figure 1.

Core components of the Hippo pathway in mammalian cells. When the Hippo pathway is ON, MST1/2 and MAP4K are activated, which subsequently phosphorylate and activate LATS1/2 kinases. Activated LATS1/2 phosphorylate transcriptional coactivator YAP/TAZ, preventing entry into the nucleus by anchoring them to 14-3-3 protein and/or promoting their degradation in the cytoplasm. This interrupts their interactions with the TEAD family of transcription factors, which subsequently change the transcription of downstream genes. When the Hippo pathway is OFF, YAP/TAZ upstream kinases are inactivated, which results in translocation of YAP/TAZ into the nucleus to interact with TEAD transcription factor to activate downstream target genes.