Fig. 2 | Signal Transduction and Targeted Therapy

Fig. 2

From: FGF/FGFR signaling in health and disease

Fig. 2

The classical FGF/FGFR pathways. Binding of appropriate growth factors to receptors triggers the conformational changes of FGFRs, resulting in dimerization and activation of FGFRs. Activated FGFRs phosphorylate FRS2a and FRS2a binds to SH2 domain-containing adaptor Grb2. Grb2 will subsequently bind to SOS, GAB1, and Cbl through its SH3 domain to activate Ras/Raf/MAPKs, including ERK MAPK, p38 MAPK, and JNK MAPK. The activated FGFRs also activate phosphatidylinositol (PI)-3 kinase and STAT. FGFRs recruit and phosphorylate PLCγ. Among the members of the FGF synexpression group, SEF and XFLRT3 are transmembrane proteins and can interact directly with FGFRs. SEF functions as a negative regulator by affecting the phosphorylation of the MAPK ERK cascade. XFLRT3 forms a complex with FGF receptors and enhances FGF/FGFR signaling. Spry acts at the level of Grb2 and/or the level of Raf to attenuate FGF/FGFR signaling. MKP3 negatively regulates FGF/FGFR signaling by dephosphorylating the activated ERK. FRS2α FGFR substrate 2α, GAB1 GRB2 associated binding protein 1, GRB2 growth factor receptor-bound 2, PKC protein kinase C, SOS son of sevenless

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