Activated FGFR2 mutants:p-FRS2 binds GRB2:GAB1:PIK3R1

Stable Identifier
R-HSA-5655320
Type
Reaction [binding]
Species
Homo sapiens
Compartment
plasma membrane, cytosol
ReviewStatus
5/5
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Activated FGFR2 mutants:p-FRS2 binds GRB2:GAB1:PIK3R1
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FGFR1-amplified cells derived from lung cancer patients show phosphorylation of AKT and S6, demonstrating the activation of the PI3K signaling pathway in these lines. Inhibition of FGFR1 phosphorylation by treatment with the in vitro reagent PD173074 did not abrogate the phosphorylation of these substrates, however, indicating that the PI3K pathway is not the major signaling pathway activated by amplified FGFR1 (Weiss, 2010; Dutt, 2011). Activation of the PI3K pathway has also been demonstrated downstream of other FGFR mutants (see for instance, Agazie, 2003; Kunii, 2008, Takeda, 2007; Byron, 2008; Demiroglu, 2001; Guasch, 2001; Chen, 2004); however not all mutants activate the PI3K pathway to the same extent and in the case of the rhabdomyosarcoma FGFR4 mutants K535 and E550, phosphorylation of AKT is actually reduced compared to wild-type signaling (Taylor, 2009).
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
17505008 AZD2171 shows potent antitumor activity against gastric cancer over-expressing fibroblast growth factor receptor 2/keratinocyte growth factor receptor

Fukuoka, K, Yamada, Y, Yanagihara, K, Nishio, K, Sasaki, H, Kimura, H, Takeda, M, Tamura, T, Komatsu, T, Yokote, H, Arao, T, Saijo, N

Clin Cancer Res 2007
18757403 Inhibition of activated fibroblast growth factor receptor 2 in endometrial cancer cells induces cell death despite PTEN abrogation

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

Cancer Res 2008
11739186 The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins

Doody, ML, Demiroglu, A, Carnicero, F, Brody, JP, Melo, JV, Koduru, P, Cross, NC, Heath, C, Hawson, G, Taylor, K, Steer, EJ, Goldman, JM, Reiter, A, Rodwell, R, Bentley, M, Allen, SL

Blood 2001
15448205 PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder

Gilliland, DG, Cohen, S, Huntly, B, Galinsky, I, Xiao, S, Duclos, N, Fabbro, D, Kutok, JL, Stone, RM, Fletcher, JA, Roesel, J, Okabe, R, Lee, BH, Chen, J, Banerji, L, Adelsperger, J, Wadleigh, M, Williams, IR, Deangelo, DJ, Meyer, T, Cohen, PS, Griffin, JD, Coburn, A

Proc Natl Acad Sci U S A 2004
14534538 The phosphotyrosine phosphatase SHP2 is a critical mediator of transformation induced by the oncogenic fibroblast growth factor receptor 3

Ischenko, I, Movilla, N, Agazie, YM, Hayman, MJ

Oncogene 2003
19809159 Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models

Chanock, SJ, Cheuk, AT, Catchpoole, D, Desai, K, Chung, JY, Chen, QR, Hewitt, SM, Fang, J, Helman, LJ, Khan, J, Kim, S, Merlino, G, Khanna, C, Mendoza, A, Ngo, V, Tsang, PS, Staudt, LM, Taylor JG, 6th, Song, YK, Shah, K, Qualman, SJ, Wei, JS, Yeung, C, Youngblood, V, Yu, Y

J Clin Invest 2009
18381441 FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival

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

Cancer Res 2008
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
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Normal reaction
Activated FGFR2:p-FRS2 binds GRB2:GAB1:PIK3R1 (Homo sapiens)
Functional status

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

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
bone development disease DOID:0080006
Authored
Rothfels, K  (2012-02-10)
Reviewed
Ezzat, S  (2012-05-15)
Created
Rothfels, K  (2014-12-05)
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