Figure 2.

Interplay between G-Protein Coupled Receptors (GPCR) signaling regulated by melatonin and GPCR signaling regulating YAP/TAZ. MT1 binding by melatonin (MLT) induces activation of associated Gαq and Gαs that leads to the accumulation of intracellular cAMP that in turn activates Protein Kinase A (PKA) and PKC. These in turn inhibit NF-κB transcriptional activity on its target promoters, including TAZ promoter. In Androgen Receptor (AR) positive cells, PKA and PKC inhibit the androgen response on AR responsive genes. In parallel, glucagon, epinephrine, and dobutamine signal through Gαs, inducing increased intracellular cAMP and activation of PKA. This in turn inhibits the RhoGTPase RhoA and activates LATS1/2 kinases, resulting in phosphorylation of YAP/TAZ, their cytoplasmic sequestration by 14-3-3 protein, their degradation mediated by βTrCP, and the impairment of their nuclear activity on pro-proliferative, pro-metastatic, and anti-apoptotic genes. ↑ indicates an increase in protein levels or activity; ↓ indicates a decrease in protein levels or activity.