Autocatalytic phosphorylation of FGFR3 fusions

Stable Identifier
Reaction [transition]
Homo sapiens
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FGFR3 fusions promote cellular proliferation and tumorigenesis that can be inhibited by tyrosine kinase inhibitors, suggesting that signaling is dependent on autophosphorylation of tyrosine residues in the intracellular region as is the case for WT FGFR3 (Singh et al, 2012; Parker et al, 2013; Williams et al, 2013; Wu et al, 2013; Yuan et al, 2014). FGFR3 fusions are reported to activate the ERK , STAT and AKT pathways, but not the PLC gamma pathway as the fusions generally lack the tyrosine residue required for PLC gamma recruitment (Parker et al, 2013; Williams et al, 2013; Wu et al, 2013; reviewed in Parker et al, 2014; Carter et al, 2015).

Literature References
PubMed ID Title Journal Year
23298836 The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma

Parker, BC, Sun, Y, Granberg, KJ, Zhang, W, Liu, CG, Ji, P, Zheng, H, Li, X, Lang, FF, Haapasalo, H, Nykter, M, Cogdell, DE, Gumin, J, Chen, K, Liu, X, Hu, L, Sawaya, R, Annala, MJ, Fuller, GN, Yli-Harja, O, Visakorpi, T

J. Clin. Invest. 2013
23175443 Oncogenic FGFR3 gene fusions in bladder cancer

Knowles, MA, Williams, SV, Hurst, CD

Hum. Mol. Genet. 2013
25467007 Careless talk costs lives: fibroblast growth factor receptor signalling and the consequences of pathway malfunction

Grose, RP, Carter, EP, Fearon, AE

Trends Cell Biol. 2015
23558953 Identification of targetable FGFR gene fusions in diverse cancers

Kalyana-Sundaram, S, Chinnaiyan, AM, Wang, R, Tomlins, SA, Ateeq, B, Cao, X, Cheng, AJ, Rhodes, DR, Hussain, MH, Kunju, LP, Lonigro, RJ, Robinson, DR, Sadis, S, Talpaz, M, Lin, SF, Pienta, KJ, Feng, FY, Roychowdhury, S, Vats, P, Wu, YM, Wyngaard, P, Su, F, Khazanov, N, Siddiqui, J, Zalupski, MM

Cancer Discov 2013
25535896 Recurrent FGFR3-TACC3 fusion gene in nasopharyngeal carcinoma

Zeng, MS, Yuan, L, Liu, ZH, Lin, ZR, Zhong, Q, Xu, LH

Cancer Biol. Ther. 2014
24588013 Emergence of FGFR family gene fusions as therapeutic targets in a wide spectrum of solid tumours

Parker, BC, Zhang, W, Annala, M, Engels, M

J. Pathol. 2014
25246530 TACC3 protein regulates microtubule nucleation by affecting γ-tubulin ring complexes

Gireesh, KK, Singh, P, Manna, TK, Thomas, GE

J. Biol. Chem. 2014
Catalyst Activity

protein tyrosine kinase activity of FGFR3 fusion dimers [plasma membrane]

Functional status

Gain of function of FGFR3 fusion dimers [plasma membrane]

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