Fig. 1

Mechanisms of physiological and oncogenic RTK activation. a Schematic representation of RTK activation in normal physiology. RTKs are activated through formation of inter-molecular dimerization in the presence of ligands, resulting in kinase activation and phosphorylation of the receptor C-terminal tail. b Schematic representation of potential gain-of-function mutations in the various subdomains of an RTK. The mutations lead to constitutive activation of the RTK, typically in the absence of ligand. c Overexpression of RTKs – often as a result of genomic amplification of the RTK gene - leads to increased local concentration of receptors