FGFR3c P250R mutant binds to ligand with enhanced affinity

Stable Identifier
R-HSA-2012074
Type
Reaction [binding]
Species
Homo sapiens
Compartment
plasma membrane, extracellular region
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FGFR3c P250R mutant binds to ligand with enhanced affinity
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FGFR3 P350R is associated with the development of Muenke syndrome, a milder craniosynostotic condition than Apert Syndrome (Bellus, 1996; Reardon, 1997). This mutation, which falls in the highly conserved Ser-Pro dipeptide in the IgII-IgIII linker, has been shown to increase the affinity of the receptor for its natural ligands, particularly for FGF9 (Ibrahimi, 2004a), without expanding the ligand-binding range of the receptor. This difference, compared to the paralogous FGFR2 S252W and P253R mutations, which bind an expanded range of ligands, is thought to account for the milder phenotype of Muenke Syndrome (Yu, 2000; Ibrahimi, 2004a, b).

Literature References
PubMed ID Title Journal Year
15282208 Biochemical analysis of pathogenic ligand-dependent FGFR2 mutations suggests distinct pathophysiological mechanisms for craniofacial and limb abnormalities

Ibrahimi, OA, Zhang, F, Eliseenkova, AV, Itoh, N, Linhardt, RJ, Mohammadi, M

Hum Mol Genet 2004
9279753 Craniosynostosis associated with FGFR3 pro250arg mutation results in a range of clinical presentations including unisutural sporadic craniosynostosis

Reardon, W, Wilkes, D, Rutland, P, Pulleyn, LJ, Malcolm, S, Dean, JC, Evans, RD, Jones, BM, Hayward, R, Hall, CM, Nevin, NC, Baraister, M, Winter, RM

J Med Genet 1997
8841188 Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes

Bellus, GA, Gaudenz, K, Zackai, EH, Clarke, LA, Szabo, J, Francomano, CA, Muenke, M

Nat Genet 1996
14613973 Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity

Ibrahimi, OA, Zhang, F, Eliseenkova, AV, Linhardt, RJ, Mohammadi, M

Hum Mol Genet 2004
11121055 Loss of fibroblast growth factor receptor 2 ligand-binding specificity in Apert syndrome

Yu, K, Herr, AB, Waksman, G, Ornitz, DM

Proc Natl Acad Sci U S A 2000
Participants
Input
Output
Participates
as an event of
Functional status

Gain of function of FGFR3c P250R [plasma membrane]

Disease Entity
Status
Disease
Name Identifier Synonyms
acrocephalosyndactylia DOID:12960 Apert syndrome
craniosynostosis DOID:2340 Premature closure of cranial sutures
Authored
Rothfels, K  (2012-02-10)
Reviewed
Ezzat, S  (2012-05-15)
Created
Rothfels, K  (2011-11-22)
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