Activated FGFR2 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange

Stable Identifier
Reaction [transition]
Homo sapiens
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Activation of Erk1/2 downstream of FGFR mutants suggests that, as is the case for WT FGFR, FGFR mutant-associated SOS1 activates RAS nucleotide exchange from the inactive GDP-bound to the active GTP-bound state (see for instance, Weiss, 2010; Dutt, 2011; Raffioni, 1998; Cha, 2009; Hart, 2000; Turner, 2010; Kunii, 2008; Byron, 2008; Roidl, 2010; Chesi, 2001; Ronchetti, 2001; reviewed in Wesche, 2011).

Literature References
PubMed ID Title Journal Year
9857065 Effect of transmembrane and kinase domain mutations on fibroblast growth factor receptor 3 chimera signaling in PC12 cells. A model for the control of receptor tyrosine kinase activation

Raffioni, S, Zhu, YZ, Bradshaw, RA, Thompson, LM

J Biol Chem 1998
18757403 Inhibition of activated fibroblast growth factor receptor 2 in endometrial cancer cells induces cell death despite PTEN abrogation

Byron, SA, Gartside, MG, Wellens, CL, Mallon, MA, Keenan, JB, Powell, MA, Goodfellow, PJ, Pollock, PM

Cancer Res 2008
19946327 The FGFR4 Y367C mutant is a dominant oncogene in MDA-MB453 breast cancer cells

Roidl, A, Foo, P, Wong, W, Mann, C, Bechtold, S, Berger, HJ, Streit, S, Ruhe, JE, Hart, S, Ullrich, A, Ho, HK

Oncogene 2010
19103595 Aberrant receptor internalization and enhanced FRS2-dependent signaling contribute to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoform

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

J Biol Chem 2009
20179196 FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer

Turner, N, Pearson, A, Sharpe, R, Lambros, M, Geyer, F, Lopez-Garcia, MA, Natrajan, R, Marchio, C, Iorns, E, Mackay, A, Gillett, C, Grigoriadis, A, Tutt, A, Reis-Filho, JS, Ashworth, A

Cancer Res 2010
21711248 Fibroblast growth factors and their receptors in cancer

Wesche, J, Haglund, K, Haugsten, EM

Biochem J 2011
18381441 FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival

Kunii, K, Davis, L, Gorenstein, J, Hatch, H, Yashiro, M, Di Bacco, A, Elbi, C, Lutterbach, B

Cancer Res 2008
11429702 Deregulated FGFR3 mutants in multiple myeloma cell lines with t(4;14): comparative analysis of Y373C, K650E and the novel G384D mutations

Ronchetti, D, Greco, A, Compasso, S, Colombo, G, Dell'Era, P, Otsuki, T, Lombardi, L, Neri, A

Oncogene 2001
21160078 Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer

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

Sci Transl Med 2010
11157491 Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma

Chesi, M, Brents, LA, Ely, SA, Bais, C, Robbiani, DF, Mesri, EA, Kuehl, WM, Bergsagel, PL

Blood 2001
21666749 Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer

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

PLoS One 2011
Catalyst Activity

guanyl-nucleotide exchange factor activity of FGFR2 mutants:p-FRS2:GRB2:SOS1 [plasma membrane]

Normal reaction
Functional status

Gain of function of FGFR2 mutants:p-FRS2:GRB2:SOS1 [plasma membrane]

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