Figure 1
From: The Hippo pathway in disease and therapy: cancer and beyond
The Hippo signalling core cassette in mammals. In response to upstream signals (coming from GPCRs and other plasma membrane associated factors), MST1/2 are activated by phosphorylation. Phosphorylated MST1/2 in complex with the scaffolding protein SAV then activates LATS1/2 kinases by phosphorylation. Activated LATS1/2, associated with their co-activator MOB1, hyperphosphorylate YAP/TAZ on different sites. These YAP/TAZ phosphorylation events create a 14-3-3 binding site that causes the cytoplasmic retention of YAP/TAZ (mediated by Ser127 phosphorylation of YAP) and a separate phospho-degron that mediates the proteasomal degradation of YAP/TAZ (mediated by Ser381 phosphorylation of YAP). When the Hippo pathway is inactive, YAP/TAZ are not phosphorylated by LATS1/2 allowing the transcriptional co-activators YAP/TAZ to accumulate in the nucleus which can result in the transcription of specific target genes involved in cell cycle, apoptosis and differentiation control. Of note, the MST1/2-LATS1/2-YAP/TAZ axis can also be influenced by additional factors (depicted as X) on each individual signalling level.