Activated FGFR3 point, translocation and fusion mutants bind FRS2

Stable Identifier
R-HSA-5655262
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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After activation, FGFR point and translocation mutants are presumed to recruit FRS2 (also known as FRS2alpha). This has been demonstrated in some cases (see for instance Ahmed, 2008; Weiss, 2010; Dutt, 2008; Dutt, 2011; Cha, 2009; Qing, 2009; Bai, 2010 ) and is inferred to occur in others by analogy with the wild-type receptor. Similarly, FGFR3 fusions appear in most cases to promote tumorigenesis and proliferation through the ERK, STAT and AKT pathways suggesting that, as is the case for the wild type receptor, FRS2 is recruited to the phosphorylated receptor (Williams et al, 2013; Parker et al, 2013; Wu et al, 2013; reviewed in Parker et al, 2014; Carter et al, 2015). In contrast, one study reports inhibition of the ERK signaling pathway by FGFR3 fusion proteins. This study supports a model in which the fusion proteins promote chromosomal instability (Singh et al, 2012).

Literature References
PubMed ID Title Journal Year
23175443 Oncogenic FGFR3 gene fusions in bladder cancer

Knowles, MA, Williams, SV, Hurst, CD

Hum. Mol. Genet. 2013
22837387 Transforming fusions of FGFR and TACC genes in human glioblastoma

Gao, Z, Sullivan, R, Niola, F, Guha, A, Zoppoli, P, Castano, A, Singh, D, Riccardi, R, Chan, JM, Finocchiaro, G, Aldape, K, Zagzag, D, Ceccarelli, M, Pellegatta, S, Porrati, P, Iavarone, A, Brat, DJ, Golfinos, JG, Rabadan, R, Qiu, K, Liu, EM, Mikkelsen, T, Reichel, J, Lasorella, A

Science 2012
18373495 Extracellular point mutations in FGFR2 elicit unexpected changes in intracellular signalling

Tregidgo, C, Suhling, K, Ladbury, JE, Ahmed, Z, Schüller, AC

Biochem J 2008
19103595 Aberrant receptor internalization and enhanced FRS2-dependent signaling contribute to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoform

Der, CJ, Harden, TK, Mitin, N, Cha, JY, Maddileti, S

J Biol Chem 2009
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
21160078 Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer

Sietsma, H, Smit, E, Solomon, B, Sollberg, S, Soltermann, A, Sos, ML, Stoelben, E, Thomas, RK, Sänger, J, Timens, W, Thunnissen, E, Wagener, P, Cappuzzo, F, Buettner, R, Brustugun, OT, Brambilla, E, Brambilla, C, Baumann, M, Beroukhim, R, Baessmann, I, Balke-Want, H, Ansén, S, Altmüller, J, Zander, T, Wright, G, Leenders, F, Koker, M, Heynck, S, Klebl, B, Heukamp, LC, Heuckmann, JM, Hallek, M, Heideman, D, Groen, H, Fischer, F, Gabler, F, Ernestus, K, Engel-Riedel, W, Damiani, S, Conron, M, Dabow, I, Clement, J, Seidel, D, Schöttle, J, Russell, P, Rauh, D, Petersen, I, Querings, S, Perner, S, Nürnberg, P, Peifer, M, Moch, H, Menon, R, Ludwig, C, Maier, S, Ligorio, C, Lorimier, P, Wolf, J, Pao, W, Weiss, J, Wainer, Z, Ullrich, RT

Sci Transl Med 2010
21666749 Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer

Mermel, C, Hammerman, PS, Greulich, H, Gray, NS, Ramos, AH, Cho, J, Chande, A, Dutt, A, Tanaka, KE, Stransky, N, Meyerson, M, Sharifnia, T

PLoS One 2011
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
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
19381019 Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice

Stephan, JP, Dornan, D, Stinson, S, Wiesmann, C, Du, X, Wu, P, Qing, J, Ashkenazi, A, Wu, Y, Tien, J, French, D, Totpal, K, Chan, P, Chen, Y, Marsters, S, Ross, S, Li, H, Wang, QR, Stawicki, S

J Clin Invest 2009
18552176 Drug-sensitive FGFR2 mutations in endometrial carcinoma

Akslen, LA, Cibulskis, K, Greulich, H, Dutt, A, Sellers, WR, Chen, TH, Winckler, W, Wyhs, N, Ziaugra, L, Zody, MC, Salvesen, HB, Meyerson, M, Stefansson, IM, Trovik, J, Wong, KK, Ramos, AH, Richter, DJ, Gabriel, S, Nicoletti, R, Onofrio, RC, Grewal, R, Hanna, M, Hatton, C, Engelsen, IB, Fennell, T

Proc Natl Acad Sci U S A 2008
20709759 GP369, an FGFR2-IIIb-specific antibody, exhibits potent antitumor activity against human cancers driven by activated FGFR2 signaling

Poling, LL, Bai, A, Chen, T, Vo, NY, Gyuris, J, Ismail, NS, Jiang, J, Weiler, S, Weng, Z, Winston, WM, Kollipara, S, Lerner, L, Mazsa, EK, Meetze, K

Cancer Res 2010
Participants
Participates
Normal reaction
Functional status

Gain of function of Activated FGFR3 point, translocation and fusion mutants [plasma membrane]

Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
bone development disease DOID:0080006
Authored
Reviewed
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