Fig. 3

Schematic overview of the Hippo signaling pathway. A “Hippo signaling ON”: activation of the Hippo pathway leads to inactivating phosphorylation and cytoplasmic retention of the co-transcriptional activators YAP1 and TAZ. Specifically, activation of mammalian sterile 20-like protein kinases 1 and 2 (MST1 and MST2) activates large tumor suppressor kinases 1 and 2 (LATS1 and 2) in partnership with their scaffold molecule Salvador Family WW Domain Containing Protein 1 (SAV1). LATS1 and 2 and their partners, MOB kinase activators 1A and B (MOB1A and MOB1B), in turn phosphorylate the co-transcriptional activators YAP1 or TAZ at several serine residues causing their inactivation. When phosphorylated at specific amino acid residues, YAP and TAZ bind the scaffold molecule 14-3-3 and are eventually transported to the proteasome for degradation. B “Hippo signaling OFF”: when the activity of the Hippo pathway is reduced, the unphosphorylated YAP and TAZ migrate to the nucleus and associate with various DNA-binding proteins, e.g., TEA domain proteins (TEAD), which control transcription of target genes