Constitutive dimerization of FGFR4 Y367C mutant

Stable Identifier
R-HSA-2012086
Type
Reaction [binding]
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
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Constitutive dimerization of FGFR4 Y367C mutant
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The Y367C mutation in FGFR4 was identified in a breast cancer cell line in a cDNA screen of kinase mutants (Ruhe, 2007). This residue is paralogous to the FGFR2 Y375C and FGFR3 Y373C mutations that have been shown to result in increased receptor activation (Prezylepa, 1996; Rousseau, 1996; d'Avis, 1998). Biochemical characterization of the FGFR4 Y367C mutation revealed that it undergoes spontaneous dimerization independent of ligand stimulation, presumably mediated by the aberrant cysteine residues in the extracellular region of the receptor (Roidl, 2009), thus affecting FGFR4 activity without directly altering its kinase activity.
Literature References
PubMed ID Title Journal Year
8696350 Fibroblast growth factor receptor 2 mutations in Beare-Stevenson cutis gyrata syndrome

Przylepa, KA, Paznekas, W, Zhang, M, Golabi, M, Bias, W, Bamshad, MJ, Carey, JC, Hall, BD, Stevenson, R, Orlow, S, Cohen MM, Jr, Jabs, EW

Nat Genet 1996
8845844 Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1)

Rousseau, F, El Ghouzzi, V, Delezoide, AL, Legeai-Mallet, L, Le Merrer, M, Munnich, A, Bonaventure, J

Hum Mol Genet 1996
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
18056464 Genetic alterations in the tyrosine kinase transcriptome of human cancer cell lines

Ruhe, JE, Streit, S, Hart, S, Wong, CH, Specht, K, Knyazev, P, Knyazeva, T, Tay, LS, Loo, HL, Foo, P, Wong, W, Pok, S, Lim, SJ, Ong, H, Luo, M, Ho, HK, Peng, K, Lee, TC, Bezler, M, Mann, C, Gaertner, S, Hoefler, H, Iacobelli, S, Peter, S, Tay, A, Brenner, S, Venkatesh, B, Ullrich, A

Cancer Res 2007
9438390 Constitutive activation of fibroblast growth factor receptor 3 by mutations responsible for the lethal skeletal dysplasia thanatophoric dysplasia type I

d'Avis, PY, Robertson, SC, Meyer, AN, Bardwell, WM, Webster, MK, Donoghue, DJ

Cell Growth Differ 1998
Participants
Input
Output
Participates
as an event of
Normal reaction
FGFR4 binds to FGF (Homo sapiens)
Functional status

Gain of function of FGFR4 Y367C [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
breast cancer DOID:1612 malignant tumor of the breast, mammary cancer, malignant neoplasm of breast, mammary tumor, primary breast cancer, breast cancer, Ca breast - NOS, breast tumor
Cross References
Mondo
Authored
Rothfels, K  (2012-02-10)
Reviewed
Ezzat, S  (2012-05-15)
Created
Rothfels, K  (2011-11-22)
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