Preferred Name |
FGFR2b mutants bind an expanded range of ligands |
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Synonyms |
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Definitions |
has a Stoichiometric coefficient of 2 Apert sydrome is the most severe of the craniosynostosis syndromes and results almost entirely from two missense mutations in the conserved Ser252 and Pro253 residues in the IgII-IgIII linker of FGFR2 (Wilkie, 1995). These mutations affect both the 'b' and 'c' isoforms, although mutation in the FGFR2c isoform is believed to be more clinically relevant to the development of Apert syndrome (Lomri, 1998). More recently, the same mutations arising somatically have been identified in endometrial and ovarian cancer (Dutt, 2008; Byron, 2008; Pollock, 2007).<br><br><br>The IgII and IgIII domains and the intervening linker of the FGF receptor constitute a binding site for FGFs (Chellaiah, 1999; Stauber, 2000; Plotnikov, 1999). The epithelial isoform FGFR2b binds only to mesenchymally expressed ligands including FGF7 and FGF10 and does not respond to epithelial ligands FGF2, 4, 6, 8 and 9 (Ornitz, 1996). Introduction of the P252W and P252R mutations into FGFR2b allows the aberrant binding and activation by the epithelially expressed ligands FGF 2, 6 and 9, establishing an autocrine signaling loop in epithelial cells. These mutations also increase the binding affinity for the receptor's normal mesenchymal ligands 2- to 8-fold (Yu, 2000; Ibrahimi, 2004b). Based on biochemical and crystal studies, the mutations in the IgII-IgIII linker region are predicted to alter the hydrogen bonding network in this region and may change the conformation and thus the ligand-binding properties of the mutant receptors (Stauber, 2000).<br> Edited: Rothfels, K, 2012-05-16 Authored: Rothfels, K, 2012-02-09 Reviewed: Ezzat, S, 2012-05-15 |
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http://purl.obolibrary.org/obo/HINO_0008127 |
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comment |
has a Stoichiometric coefficient of 2 Apert sydrome is the most severe of the craniosynostosis syndromes and results almost entirely from two missense mutations in the conserved Ser252 and Pro253 residues in the IgII-IgIII linker of FGFR2 (Wilkie, 1995). These mutations affect both the 'b' and 'c' isoforms, although mutation in the FGFR2c isoform is believed to be more clinically relevant to the development of Apert syndrome (Lomri, 1998). More recently, the same mutations arising somatically have been identified in endometrial and ovarian cancer (Dutt, 2008; Byron, 2008; Pollock, 2007). Edited: Rothfels, K, 2012-05-16 Authored: Rothfels, K, 2012-02-09 Reviewed: Ezzat, S, 2012-05-15 |
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definition source |
Pubmed18552176 Pubmed10574949 Pubmed20106510 Reactome, http://www.reactome.org Pubmed9502772 Pubmed7719344 Pubmed11121055 Pubmed10618369 Pubmed18757403 Pubmed8663044 Pubmed15282208 Pubmed17525745 Pubmed10490103 |
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has input |
http://purl.obolibrary.org/obo/HINO_0004844 |
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has output | ||
label |
FGFR2b mutants bind an expanded range of ligands |
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name |
FGFR2b somatic mutants bind an expanded range of ligands |
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prefixIRI |
HINO:0008127 |
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prefLabel |
FGFR2b mutants bind an expanded range of ligands |
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seeAlso |
Reactome Database ID Release 432033474 ReactomeREACT_120790 |
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subClassOf |