Fibroblast growth factor receptor 3 (FGFR3) is the only gene known to cause achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric dysplasia types I and II (TD I and TD II). A second, as yet unidentified, gene also causes HCH. In this study, we used sequencing analysis to determine the frequency of FGFR3 mutations for each phenotype in 324 cases from the International Skeletal Dysplas...

Fibroblast growth factor receptors (FGFRs) are activated by mutation and overexpressed in bladder cancers (BCs), and FGFR inhibitors are currently being evaluated in clinical trials in BC patients. However, BC cells display marked heterogeneity in their responses to FGFR inhibitors, and the biological mechanisms underlying this heterogeneity are not well defined. Here we used a novel inhibitor ...

Missense mutations in fibroblast growth factor receptor 3 (FGFR3) result in several human skeletal dysplasias, including the most common form of dwarfism, achondroplasia. Here we show that a glycine-to-cysteine substitution at position 375 (Gly375Cys) in human FGFR3 causes ligand-independent dimerization and phosphorylation of FGFR3 and that the equivalent substitution at position 369 (Gly369Cy...

The fibroblast growth factor receptor 3 (FGFR3) is a protein belonging to the family of receptor tyrosine kinases. FGFR3 plays an important role in human skeletal development. Mutations in this protein, including Gly380Arg or Ala391Glu substitutions in the transmembrane (TM) region, can cause different disorders in bone development. The determination of the spatial structure of the FGFR3 TM dom...

OBJECTIVE Head and neck squamous cell carcinoma, including oral squamous cell carcinoma (OSCC) is the sixth most common cancer in the human population. Despite significant efforts committed in treatment of OSCC the overall survival rate of OSCC has not improved significantly. Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) genes are responsible for some human cancers, in...

Fibroblast growth factor receptor (FGFR) signaling is transduced by the mitogen-activated protein kinase (MAPK) cascade and the signal transducers and activators of transcription (STATs). Suppressors of cytokine signaling (SOCS) proteins are expressed in response to cytokine-inducible stimulation of STAT phosphorylation, acting in a negative-feedback mechanism to hinder the activities of these ...

Several gain-of-function mutations in a receptor tyrosine kinase, fibroblast growth factor receptor 3 (FGFR3), cause dwarfism in humans. Two particularly severe dwarfisms, thanatophoric dysplasia type II (TDII) and severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), are associated with glutamic acid (E) and methionine (M) substitutions at the K650 residue in the ki...

PURPOSE We previously showed that Discs large-1 (Dlg-1) regulates lens fiber cell structure and the fibroblast growth factor receptor (Fgfr) signaling pathway, a pathway required for fiber cell differentiation. Herein, we investigated the mechanism through which Dlg-1 regulates Fgfr signaling. METHODS Immunofluorescence was used to measure levels of Fgfr1, Fgfr2, and activated Fgfr signaling ...

Gattineni J, Twombley K, Goetz R, Mohammadi M, Baum M. Regulation of serum 1,25(OH)2Vitamin D3 levels by fibroblast growth factor 23 is mediated by FGF receptors 3 and 4. Am J Physiol Renal Physiol 301: F371–F377, 2011. First published May 11, 2011; doi:10.1152/ajprenal.00740.2010.—Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in the pathogenesis of several hypophosph...

Activating mutations of the p110 alpha subunit of PI3K (PIK3CA) oncogene have been identified in a broad spectrum of malignant tumors. However, their role in benign or preneoplastic conditions is unknown. Activating FGF receptor 3 (FGFR3) mutations are common in benign skin lesions, either as embryonic mutations in epidermal nevi (EN) or as somatic mutations in seborrheic keratoses (SK). FGFR3 ...