Autocatalytic phosphorylation of FGFR1 mutants with enhanced kinase activity

has a Stoichiometric coefficient of 16 The three kinase domain mutants of FGFR1 that have been identified in glioblastoma are predicted or have been shown to result in enhanced kinase activity. The N546K (Rand, 2005) residue lies in a stretch of 9 amino acids that are conserved between all four FGFRs. Mutation of the paralogous residue in FGFR3 (N540K) has been shown to result in weak ligand-independent contstitutive activation in the autosomal disorder hypochodroplasia (Raffioni, 1998). In FGFR2 mutation of the paralogous residue to lysine has been identified in endometrial cancer and been shown to result in enhanced kinase activity (Dutt, 2008; Pollock, 2008); germline mutations at this site in FGFR2 are also associated with the development of Crouzon and Pfeiffer syndromes (Kan, 2002). The FGFR1 N546K mutations has accelerated rates of autophosphorylation and supports transformation when transfected into Rat-1 cells (Lew, 2009).<br><br><br>The FGFR1 K656E (TCGA, 2008) mutation is paralogous to activating mutations in FGFR3 kinase domain associated with the development of thanatophoric dysplasias (Tavormina, 1999; Bellus, 2000; Hart, 2000), and has itself been shown to activating when expressed in neural crest cells (Petiot, 2002).<br><br><br>The FGFR1 R576W (Rand, 2005) mutation increases the hydrophobicity of the receptor, and is postulated to enhance protein-protein interactions and thereby increase the likelihood of autophosphorylation of adjacent tyrosine residues, although this has not been explicitly demonstrated.<br><br><br> Edited: Rothfels, K, 2012-05-16 Authored: Rothfels, K, 2012-02-09 Reviewed: Ezzat, S, 2012-05-15

http://purl.obolibrary.org/obo/HINO_0008121

has a Stoichiometric coefficient of 16

The three kinase domain mutants of FGFR1 that have been identified in glioblastoma are predicted or have been shown to result in enhanced kinase activity. The N546K (Rand, 2005) residue lies in a stretch of 9 amino acids that are conserved between all four FGFRs. Mutation of the paralogous residue in FGFR3 (N540K) has been shown to result in weak ligand-independent contstitutive activation in the autosomal disorder hypochodroplasia (Raffioni, 1998). In FGFR2 mutation of the paralogous residue to lysine has been identified in endometrial cancer and been shown to result in enhanced kinase activity (Dutt, 2008; Pollock, 2008); germline mutations at this site in FGFR2 are also associated with the development of Crouzon and Pfeiffer syndromes (Kan, 2002). The FGFR1 N546K mutations has accelerated rates of autophosphorylation and supports transformation when transfected into Rat-1 cells (Lew, 2009).


The FGFR1 K656E (TCGA, 2008) mutation is paralogous to activating mutations in FGFR3 kinase domain associated with the development of thanatophoric dysplasias (Tavormina, 1999; Bellus, 2000; Hart, 2000), and has itself been shown to activating when expressed in neural crest cells (Petiot, 2002).


The FGFR1 R576W (Rand, 2005) mutation increases the hydrophobicity of the receptor, and is postulated to enhance protein-protein interactions and thereby increase the likelihood of autophosphorylation of adjacent tyrosine residues, although this has not been explicitly demonstrated.

Edited: Rothfels, K, 2012-05-16

Authored: Rothfels, K, 2012-02-09

Reviewed: Ezzat, S, 2012-05-15

Pubmed18552176

Pubmed18772890

Pubmed11781872

Reactome, http://www.reactome.org

Pubmed19224897

Pubmed12112473

Pubmed16186508

Pubmed10918587

Pubmed17525745

Pubmed10053006

Pubmed9857065

http://purl.obolibrary.org/obo/HINO_0017086

http://purl.obolibrary.org/obo/CHEBI_15422

http://purl.obolibrary.org/obo/HINO_0017085

http://purl.obolibrary.org/obo/CHEBI_16761

Autocatalytic phosphorylation of FGFR1 mutants with enhanced kinase activity

HINO:0008121

Autocatalytic phosphorylation of FGFR1 mutants with enhanced kinase activity

EC Number: 2.7.10

ReactomeREACT_120859

Reactome Database ID Release 432023460

http://purl.obolibrary.org/obo/INO_0000040