Participate in the pathway References
Rho-ROCK1 signaling pathway As a nuclear transmission mechanical signal, YAP/TAZ activity is triggered by ECM stiffness and cell shape, which is regulated by Rho GTPase activity and actomyosin cytoskeletal tension. When ROCK1 is activated by RhoA-GTP, various proteins, such as myosin light chain, are phosphorylated, resulting in a decrease in free globular actin, actin aggregation, and the appearance of stress fibers [65,66].
TGF-β signaling pathway In human dermal fibroblasts, YAP/TAZ cooperates with the transcription factors AP-1 and Smad7 to regulate TGF-β signaling. Decreased YAP/TAZ levels lead to activation of AP-1 activity, which induces Smad7 and inhibits the TGF-β pathway [15,67,68].
PI3K signaling pathway The Hippo tumor suppressor pathway restricts growth factor receptor signaling through the PI3K pathway, and YAP/TAZ acts as a redundant regulator of the PI3K/AKT pathway [15,69].
GPCR signaling pathway Conjugation of GPCRs to Gα12/13, Gαq/11 or Gαi/o (e.g., LPA, thrombin receptors) activates YAP/TAZ. Conversely, GPCRs coupling to Gαs (e.g., epinephrine and glucagon receptors) inhibit YAP/TAZ [15,70].
KRAS signaling pathway KRAS induces posttranscriptional modification of YAP/TAZ and enhances its transcriptional activity through the MAPK pathway [15,71].
EGFR signaling pathway YAP/TAZ silencing reduces maintenance of resistance, whereas YAP/TAZ overexpression reduces the responsiveness of sensitive parental cells to EGFR inhibitors [72,73].