Fig. 2. Hippo signaling pathway. Schematic diagram for the core components and signal transduction of Hippo pathway. (A) When Hippo signaling is Off (in low cell density): The kinases MST1/2 and LATS are inactive, which results in inhibition of phosphorylation of YAP and TAZ. The stabilized YAP/TAZ in nuclei interacts with TEAD and enhances the transcription of target genes related to anti-apoptosis and proliferation. (B) When Hippo signaling is On (in high cell density): Activation of KIBRA and NF2 via unknown upstream signaling leads to activation of MST1/2. Activated MST1/2 phosphorylate SAV1 which in turn phosphorylate LATS and MOB1. The activated LATS/MOB phosphorylates YAP/TAZ which results in cytoplasmic retention by 14-3-3 protein and proteasomal degradation of YAP/TAZ. As a result, TEAD interacts with VGL4 and suppresses the expression of target genes.