Cytosolic FGFR1 fusion proteins bind PIK3R1

Stable Identifier
Reaction [omitted]
Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
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

Borg, JP, Guasch, G, Birnbaum, D, Pébusque, MJ, Ollendorff, V

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

Doody, ML, Demiroglu, A, Carnicero, F, Brody, JP, Melo, JV, Koduru, P, Cross, NC, Heath, C, Hawson, G, Taylor, K, Steer, EJ, Goldman, JM, Reiter, A, Rodwell, R, Bentley, M, Allen, SL

Blood 2001
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

Gilliland, DG, Cohen, S, Huntly, B, Galinsky, I, Xiao, S, Duclos, N, Fabbro, D, Kutok, JL, Stone, RM, Fletcher, JA, Roesel, J, Okabe, R, Lee, BH, Chen, J, Banerji, L, Adelsperger, J, Wadleigh, M, Williams, IR, Deangelo, DJ, Meyer, T, Cohen, PS, Griffin, JD, Coburn, A

Proc Natl Acad Sci U S A 2004
18412956 Myeloproliferative disorder FOP-FGFR1 fusion kinase recruits phosphoinositide-3 kinase and phospholipase Cgamma at the centrosome

Tassin, AM, Lelièvre, H, Chevrier, V, Birnbaum, D

Mol Cancer 2008
15050920 Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations

Krause, DS, Dimitri, CA, Asiedu, F, Van Etten, RA, Cross, NC, Roumiantsev, S, Neumann, CA

Cancer Cell 2004
Functional status

Gain of function of cytosolic p-FGFR1 fusion mutant dimers [cytosol]

Disease Entity
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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