Figure 1.

Signal transduction network of Hippo pathway. Cells respond to mechanical forces, cell polarity, and adhesion signals by adjusting their tensional state and actin dynamics to regulate the activity of Hippo pathway components. When a cell adheres to a larger area or grows on a harder ECM, causes the activation of integrin signaling, and promotes the assembly of FAK/Src complex, which inactivate LATS1/2 and facilitate the polymerization of F-actin cytoskeleton via Rho-GTPases, F-actin then induces the dephosphorylation and guides the nuclear translocation of YAP/TAZ. GPCR signaling responds to a variety of activators (energy, proteins, lipids, sugars), and performs the same function by acting on RHO-GTPases. Hypo-phosphorylated YAP and TAZ accumulate in the nucleus where they can bind to various TFs, most notably the TEAD family, to direct gene expression changes that control a range of biological events. Pointed and blunt arrowheads indicate activating and inhibitory interactions, respectively. FAK, Focal adhesion kinase; GPCRs, G-protein-coupled receptors; LATS, Large tumor suppressor; MST, Mammalian sterile 20 like; Src, steroid receptor coactivator; TEAD, TEA domain protein; TFs, transcription factors; YAP/TAZ, yes-associated protein/transcriptional coactivator with PDZ-binding motif.