Activated FGFR1 mutants and fusions bind PLCG1

Stable Identifier
Reaction [binding]
Homo sapiens
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Although it has not been rigourously established, there is some evidence that PLC-gamma signaling may be activated after autophosphorylation of some FGFR mutants, analagous to the wild type receptor (see for instance, Hart, 2000; Chen, 2005; Cha, 2008; di Martino, 2009; Gartside, 2009; Cross, 2000; Hatch, 2006). The extent to which each of the mutants activates this pathway and to which proliferation and tumorigenesis relies on PLC-gamma dependent signaling, remains to be more firmly established. 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 (Guasch, 2001; Roumiantsev, 2004, Lelievre, 2008, Chase, 2007). In the case of BCR-FGFR1 and ZMYM2-FGFR1, mutation of the PLCgamma binding site significantly decreased the transformative phenotype of the FGFR1 fusion (Roumiantsev, 2004).
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
18337450 Involvement of fibroblast growth factor receptor 2 isoform switching in mammary oncogenesis

Der, CJ, Cha, JY, Lambert, QT, Reuther, GW

Mol Cancer Res 2008
16091734 FGFR3 as a therapeutic target of the small molecule inhibitor PKC412 in hematopoietic malignancies

Gilliland, DG, Cohen, S, Huntly, BJ, Griffin, J, Duclos, N, Fabbro, D, Okabe, R, Moore, S, Mitsiades, CS, Lee, BH, Chen, J, Kutok, J, Adelsperger, J, Anderson, KC, Coburn, A, Williams, I

Oncogene 2005
10918587 Transformation and Stat activation by derivatives of FGFR1, FGFR3, and FGFR4

Tynan, JA, Donoghue, DJ, Hart, KC, Kanemitsu, MY, Robertson, SC, Meyer, AN

Oncogene 2000
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
19749790 Mutant fibroblast growth factor receptor 3 induces intracellular signaling and cellular transformation in a cell type- and mutation-specific manner

Knowles, MA, di Martino, E, L'Hote, CG, Tomlinson, DC, Kennedy, W

Oncogene 2009
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
10652257 Tyrosine 766 in the fibroblast growth factor receptor-1 is required for FGF-stimulation of phospholipase C, phospholipase D, phospholipase A(2), phosphoinositide 3-kinase and cytoskeletal reorganisation in porcine aortic endothelial cells

Landgren, E, Hodgkin, MN, Roberts, S, Cross, MJ, Claesson-Welsh, L, Wakelam, MJ

J Cell Sci 2000
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
19147536 Loss-of-function fibroblast growth factor receptor-2 mutations in melanoma

Pollock, PM, Eliseenkova, AV, Wellens, CL, Curtis, AV, Gartside, MG, Bastian, BC, Byron, SA, Bengston, A, Riedesel, E, Mann, GJ, Harper, UL, Yudt, LM, Hyder, P, Chen, H, Mohammadi, M, Meltzer, PS, Ibrahimi, OA, Ma, J, Trent, JM, Curtin, JA

Mol Cancer Res 2009
16844695 Intracellular retention, degradation, and signaling of glycosylation-deficient FGFR2 and craniosynostosis syndrome-associated FGFR2C278F

Hatch, NE, Hudson, M, Cunningham, ML, Seto, ML, Bothwell, M

J Biol Chem 2006
Functional status

Gain of function of Activated FGFR1 mutants and fusions [plasma membrane]

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