Autocatalytic phosphorylation of FGFR2b mutants with enhanced ligand binding

Stable Identifier
Reaction [transition]
Homo sapiens
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After aberrantly dimerizing in response to epithelially expressed ligands, FGFR2b S252W and P253R mutants are assumed to undergo transautophosphorylation analagous to both the wild-type receptor, although this has not been explicitly demonstrated. Transformation of NIH 3T3 cells with the FGFR2b S252W mutant confers anchorage independent growth and results in increased phosphorylation of FRS2 in a manner that depends on a functional kinase domain (Dutt, 2008). Knock-down or chemical inhibition of other FGFR2-activating mutations identified in endometrial cancer cells has been shown to cause cell death (Byron, 2008).

Literature References
PubMed ID Title Journal Year
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
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
Catalyst Activity

protein tyrosine kinase activity of FGFR2b mutant dimers with enhanced ligand-binding bound to FGFs [plasma membrane]

Functional status

Gain of function of FGFR2b mutant dimers with enhanced ligand-binding bound to FGFs [plasma membrane]

Disease Entity
Name Identifier Synonyms
female reproductive endometrioid cancer DOID:3001 endometrioid tumor (morphologic abnormality), endometrioid neoplasm
ovarian cancer DOID:2394 ovarian neoplasm, malignant tumour of ovary, neoplasm of ovary (disorder), ovary neoplasm, primary malignant neoplasm of ovary and other uterine adnexa (disorder), ovarian cancer, tumor of the Ovary, ovary cancer, malignant Ovarian tumor, primary ovarian cancer, malignant tumor of ovary (disorder)
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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