Fig. 1.

Classical model of RTK activation mechanism. Upon ligand binding, RTKst undergo dimerization and trans-autophosphorylation of the kinase insert. The juxtamembrane domain, activation loop and the C-terminal tail are dislocated away from the kinase activation site, so ATP binding and phosphorylation can take place. This causes secondary transphosphorylations (shown in “RTKIs and cancer therapy” section) in the RTK kinase domains, creating docking sites for the binding of different intracellular signal proteins involved in cell growth, proliferation, and metastasis-associated signaling cascades