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. 2017 Sep 6;18(9):1913. doi: 10.3390/ijms18091913

Figure 3.

Figure 3

Interplay between melatonin, YAP/TAZ, and metabolic pathways. Melatonin (MLT) upregulates glucagon production and downregulates insulin production and signaling. Glucagon inhibits YAP/TAZ nuclear function through Gαs signaling. Conversely, insulin and GPCR signaling synergize to positively regulate nuclear YAP onto YAP/TEAD target genes. In addition, YAP/TAZ activate AKT and mTOR, which are part of the insulin signaling. In conclusion, melatonin may inhibit YAP/TAZ nuclear function by inducing glucagon expression and decreasing insulin expression. On the other hand, YAP/TAZ positively regulate insulin signaling, and, vice versa, insulin signaling positively regulates YAP, suggesting an antagonism between melatonin function and nuclear YAP/TAZ function. Arrows indicate activation, while dashed and blunt lines indicate inhibition. The figure also shows the interaction between the insulin receptor scaffold 4 (IRS4) with insulin receptor, integrins, and MT1/2 receptors potentially linking these transmembrane proteins at the cell membrane. IR = Insulin Receptor, IRS1/2/4 = insulin receptor scaffold 1/2/4.