Fig. 8: Models for the signaling transduction of fusion chimeras and targeted drugs working in the downstream of FGF signal pathway.

Normal biological processes of FGF signal pathway (a). Sub-classical and classical chimeras lead to formation of a fusion protein consisting of a transcription factor fused to an FGFR kinase domain with consequent FGFR dimerization and activation leading to ligand-independent FGF signaling. Non-classical fusion cannot active downstream signal pathway. SMKIs suppressed the phosphorylation of FRS2, AKT, and MAPK then confer anchorage-independent growth and in vivo tumorigenesis (b).
represents Ig-like domain of FGFR2,
represents tyrosine kinase domain of FGFR2,
represents phosphorylation, and
represents stimulating target gene activity.