Figure 7. Scheme of the proposed mechanism of action of Fumos.

EGF induces the activation of EGFR. Subsequently, Gab1 is associated with the activated EGFR, and Shp2 can dephosphorylate Gab1 on RasGAP binding sites disengaging RasGAP from Ras activation³⁹. The PTP activity of Shp2 is required for full activation of Ras. Fumos inhibits the Gab1-Shp2 interaction leading to downregulate the acitivation of Ras-ERK. Shp2 also induces the activation of Src by increasing autophosphorylation at Tyr416 and dephosphorylating the inhibitory site Tyr530, which leading to the phosphorylation of paxillin⁴⁵. Fumos inhibits Src activation by downregulating the phosphorylation of Src and paxillin. The red X symbol represents the effective site of Fumos.