Reciprocal regulation of YAP activity by TRIO-RAC1 signaling and the Hippo pathway. RUNX3 interacts with YAP and TEAD4 to form a YAP-TEAD4-RUNX3 ternary complex. When TRIO-RAC signaling is activated, kinase activity of LATS is inhibited while YAP activity is increased. RUNX3 then dissociates from the ternary complex, resulting in the formation YAP-TEAD complex. When cell growth is inhibited, TEAD dissociates from the ternary complex through LATS-mediated YAP phosphorylation, resulting in the formation YAP-RUNX3 complex. Therefore, LATS1/2-mediated YAP phosphorylation not only inhibits YAP-TEAD complex, but also facilitates YAP-RUNX3 complex formation.
