Figure 1.

Schematic representation of the structures of human c-MET, RON, and potential signaling inhibition strategies. Mature c-Met/RON composed of an extracellular α-chain and a transmembrane β-chain with intrinsic tyrosine kinase (TK) activity. The extracellular sequences of c-MET/RON contain several functional domains, including sema, PSI and immunoglobulin-like plexin transcription (IPT) units. Binding of HGF or MSP results in the c-MET/RON auto-phosphorylation of several tyrosine residues in the kinase activation loop or in the C-terminal tail, which increases enzymatic activities. These activities stimulate intracellular signaling cascades and lead to increased cellular activities. Different strategies using various candidate therapeutic agents were applied to block c-MET/RON signaling pathways.