Fig. 1.

The core of the Hippo pathway. Multiple upstream signals regulate phosphorylation when the Hippo signaling pathway is activated, and MST1/2 kinases and SAV1 form a complex to phosphorylate and activate LATS1/2. YAP/TAZ proteins, two important downstream effectors of the Hippo pathway, are phosphorylated by LATS1/2 kinases. Phosphorylation of YAP/TAZ triggers the recruitment of 14-3-3 proteins, which promote cytoplasmic retention or proteolytic destruction. YAP/TAZ is not phosphorylated, localizes to the nucleus, forms a complex with transcription factor TEADs, and controls genes needed for endothelial cell proliferation, migration, and survival when the Hippo signaling pathway is turned off. LATS1/2 large tumor suppressor kinase; MST1/2 mammalian ste20-like kinase; SAV1 scaffold protein salvador; TAZ transcriptional co-activator with PDZ-binding motif; TEAD TEA domain family member; YAP Yes-associated protein