Figure 2.

Schematic representation of the mammalian Hippo signaling pathway. Large Tumor Suppressor kinases (LATS1/2) can be activated by a variety of signals, including by mammalian Hippo kinases MST1/2 or other upstream kinases (MAP4Ks), by G-protein coupled receptor (GPCR)-mediated modulation of Rho family GTPase activities and/or actin cytoskeleton remodeling, and by NF2-mediated membrane recruitment. In turn, activated LATS1/2 phosphorylate and inactivate YES-associated protein (YAP) on Ser127 and transcriptional co-activator with PDZ-binding motif (TAZ) on Ser89. YAP/TAZ are transcriptional co-activators that interact with DNA binding transcription factors (TFs), such as TEADs, to initiate gene expression programs. Cell junctional α-catenin (α-CAT) or angiomotin (AMOT) inactivate YAP/TAZ by activating LATS1/2 and by localizing YAP/TAZ to cell junctions. Conversely, loss of cell-cell contacts activates Yap/TAZ-mediated pro-tumorigenic gene expression