Phosphorylation of cytosolic FGFR1 fusion dimers

Stable Identifier
Reaction [transition]
Homo sapiens
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After ligand-independent dimerization, FGFR1 fusions are trans-autophosphorylated on tyrosine residues (see for instance Popovici, 1998; Ollendorff, 1999; Guasch, 2000). Although the sites of tyrosine phosphorylation have not been mapped in the context of the fusion proteins, at least some of the same residues appear to be phosphorylated as in full length FGFR1. For instance, phospho-specific antibodies have demonstrated that TRIM24 is phosphorylated on Y653 and Y654, the activation loop tyrosines of FGFR1 (Belloni, 2005). Likewise, FGFR1 fusions with ZMYM2, BCR, FGFR1OP and TRIM24 all result in recruitment and phosphorylation of PLCgamma, and where mutational studies have been performed, mutation of the PLCgamma binding site Y766 has been shown to abrogate this signaling (Roumiantsev, 2004, Lelievre, 2008, Chase, 2007). In the case of BCR-FGFR1, the BCR moiety of the fusion protein has also been shown to be phosphorylated on at least one tyrosine residue, Y177, which results in the recruitment of GRB2 (Roumiantsev, 2004).
Literature References
PubMed ID Title Journal Year
15609342 8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes

Di Fiore, PP, Gasparini, P, Belloni, E, Trubia, M, Tapinassi, C, Nuciforo, P, Micucci, C, Martino, B, Pelicci, PG, Confalonieri, S, Lo-Coco, F

Genes Chromosomes Cancer 2005
17698633 Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome

Grand, FH, Cross, NC, Chase, A

Blood 2007
9576949 Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13)

Leroux, D, Jacrot, M, Guasch, G, Chaffanet, M, Adelaide, J, Birnbaum, D, Pébusque, MJ, Popovici, C, Ollendorff, V

Proc Natl Acad Sci U S A 1998
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
10688839 FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33)

Guasch, G, Mack, GJ, Birnbaum, D, Dastugue, N, Pébusque, MJ, Rattner, JB, Popovici, C

Blood 2000
10480903 Characterization of FIM-FGFR1, the fusion product of the myeloproliferative disorder-associated t(8;13) translocation

Guasch, G, Galindo, R, Isnardon, D, Birnbaum, D, Pébusque, MJ, Ollendorff, V

J Biol Chem 1999
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
Catalyst Activity

protein tyrosine kinase activity of cytosolic FGFR1 fusion mutant dimers [cytosol]

Functional status

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

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