GRB2:GAB1:PI3Kreg binds to p-FRS2:activated FGFR mutants Authored: Rothfels, K, 2012-02-09 Edited: Rothfels, K, 2012-05-16 FGFR1-amplified cells derived from lung cancer patients show phosphorylation of AKT and S6, demonstrating the activation of the PI3K signaling pathway in these lines. Inhibition of FGFR1 phosphorylation by treatment with the in vitro reagent PD173074 did not abrogate the phosphorylation of these substrates, however, indicating that the PI3K pathway is not the major signaling pathway activated by amplified FGFR1 (Weiss, 2010; Dutt, 2011). Activation of the PI3K pathway has also been demonstrated downstream of other FGFR mutants (see for instance, Agazie, 2003; Kunii, 2008, Takeda, 2007; Byron, 2008; Demiroglu, 2001; Guasch, 2001; Chen, 2004); however not all mutants activate the PI3K pathway to the same extent and in the case of the rhabdomyosarcoma FGFR4 mutants K535 and E550, phosphorylation of AKT is actually reduced compared to wild-type signaling (Taylor, 2009). Pubmed11689702 Pubmed11739186 Pubmed14534538 Pubmed15448205 Pubmed17505008 Pubmed18381441 Pubmed18757403 Pubmed19809159 Pubmed21160078 Pubmed21666749 Reactome Database ID Release 431986643 Reactome, http://www.reactome.org ReactomeREACT_121102 Reviewed: Ezzat, S, 2012-05-15 GRB2:GAB1:PIK3R1 Activated FGFR mutants:p-FRS2alpha Activated FGFR mutants:p-FRS2alpha:GRB2:GAB1:PIK3R1