Autocatalytic phosphorylation of FGFR2 ligand-independent mutants

Stable Identifier
Reaction [transition]
Homo sapiens
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FGFR2 S267P undergoes ligand-independent dimerization, and appears unable to stably bind FGF2 ligand under the conditions examined (Anderson, 1998). FGFR2b S373C and Y376C are paralogous to the FGFR3 S371C and Y373C mutations that are seen in thanatophoric dysplasia I (Rousseau, 1996; Tavormina, 1995a) and which have been shown to undergo spontaneous dimerization in the absence of ligand (d'Avis, 1998; Adar, 2002). Moreover, other FGFR2 mutations that introduce unpaired cysteine residues have been shown to support formation of intermolecular disulphide bonds (Galvin, 1996; Neilson and Friesel, 1995), supporting the notion that the FGFR2b S373C and Y376C mutants may promote spontaneous receptor dimerization and activation.
Literature References
PubMed ID Title Journal Year
7647778 Stop codon FGFR3 mutations in thanatophoric dwarfism type 1

Bonaventure, J, Munnich, A, Narcy, F, Rousseau, F, Sanak, M, Saugier, P, Le Merrer, M, Delezoide, AL, Maroteaux, P

Nat Genet 1995
7773297 Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3

Wilcox, WR, Lachman, RS, Cohn, DH, Wasmuth, JJ, Thompson, LM, Wilkin, DJ, Rimoin, DL, Shiang, R, Zhu, YZ, Tavormina, PL

Nat Genet 1995
9700203 Apert syndrome mutations in fibroblast growth factor receptor 2 exhibit increased affinity for FGF ligand

Anderson, J, Enriquez-Harris, P, Heath, JK, Burns, HD, Wilkie, AO

Hum Mol Genet 1998
8755573 Constitutive receptor activation by Crouzon syndrome mutations in fibroblast growth factor receptor (FGFR)2 and FGFR2/Neu chimeras

Galvin, BD, Donoghue, DJ, Hart, KC, Webster, MK, Meyer, AN

Proc Natl Acad Sci U S A 1996
12009017 Differential activation of cysteine-substitution mutants of fibroblast growth factor receptor 3 is determined by cysteine localization

Yayon, A, David, P, Monsonego-Ornan, E, Adar, R

J Bone Miner Res 2002
9438390 Constitutive activation of fibroblast growth factor receptor 3 by mutations responsible for the lethal skeletal dysplasia thanatophoric dysplasia type I

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

Cell Growth Differ 1998
8798788 Ligand-independent activation of fibroblast growth factor receptors by point mutations in the extracellular, transmembrane, and kinase domains

Friesel, R, Neilson, KM

J Biol Chem 1996
Catalyst Activity

protein tyrosine kinase activity of FGFR2 ligand-independent mutant dimers [plasma membrane]

Functional status

Gain of function of FGFR2 ligand-independent mutant dimers [plasma membrane]

Disease Entity
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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