Activation of the PI3K signaling pathway has been demonstrated for a number of FGFR1 fusion proteins and inhibitors of this pathway impair the proliferative and survival function of the fusions (Guasch, 2001; Demiroglu, 2001; Chen, 2004; Lelievre, 2008). FGFR1 fusions lack the FRS2-binding site of the full length protein, so the mechanism of PI3K recruitment is unclear. Unlike BCR-FGFR1, which has been shown to recruit GRB2 through the BCR Y177 site, GRB2 did not co-precipitate with the ZMYM2-FGFR1 fusion (Roumianetsev, 2004). In the case of FOP-FGFR1, Y730 has been shown to be required for the recruitment of the p85 subunit of PI3K; however, CEP110-FGFR1, which contains Y730 in the context of the same pYXXM motif, was not shown to recruit p85 at the centrosome (Guasch, 2001).
|cancer||162||[malignant tumor, malignant neoplasm, primary cancer]|
|18412956||Myeloproliferative disorder FOP-FGFR1 fusion kinase recruits phosphoinositide-3 kinase and phospholipase Cgamma at the centrosome||Mol Cancer||2008|
|15448205||PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder||Proc Natl Acad Sci U S A||2004|
|11689702||8p12 stem cell myeloproliferative disorder: the FOP-fibroblast growth factor receptor 1 fusion protein of the t(6;8) translocation induces cell survival mediated by mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt/mTOR pathways||Mol Cell Biol||2001|
|11739186||The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins||Blood||2001|
|15050920||Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations||Cancer Cell||2004|