Fig. 4

FGFR fusions. A Schematic representations of FGFR type I/II fusions. Fusions of FGFR with genes that encode other signaling proteins at N- terminal (type I) or C- terminal (type II) result in release of autoinhibition state and followed by aberrant kinase activation. B Potential oncogenic mechanisms of FGFR fusions. Left: fusions produce elevated oncogenic signaling through promoter exchange and FGFR overexpression. Middle: ligand-independent FGFR oligomerization lead to constitutively activation of FGFR kinase mediated by the PPIs through the oligomerization domain (OD) within the fusion partners. Right: FGFR fusion oncoproteins may undergo a higher-order assembly to produce membraneless cytoplasmic protein granules that promote local RAS activation and induce MAPK signaling activation in cancer. TM, transmembrane region; TK, tyrosine kinase domain