Figure 10
From: Activation state-dependent interaction between Gαq subunits and the Fhit tumor suppressor
Distinct regulations of Fhit by G q - and EGF-dependent pathways. Agonist binding to Gq-coupled receptor leads to Gαq activation and dissociation with Gβγ complex. Activated Gαq can interact with Fhit and stabilize it, which results in increased Fhit level and consequent enhancement of the growth suppressive effect of Fhit. On the other hand, activation of the EGF receptor stimulates Src-mediated phosphorylation of Fhit at the Tyr114 site. The phosphorylated Fhit undergoes degradation which leads to a decrease in the Fhit protein level as well as the tumor suppressive effect of Fhit. Although activated Gαq also stimulates Src-mediated Fhit Tyr114 phosphorylation, the overall Fhit protein amount is increased rather than decreased, indicating that either an additional signal is required for the induction of Fhit degradation (which is concomitantly generated by EGF but not by activated Gαq; indicated as a dashed line) or activated Gαq can up-regulate Fhit via stabilization.