FGFR3

GWB-58A1B8

Synthetic peptide: AEEELVEADEAGSVK conjugated with glutaraldehyde to KLH corresponding to amino acids 359-372 of Human FGFR3 with a C-terminal.

No reaction with human FGFR1 and FGFR2 is detected.

FGFR3

1 mg/ml

15mM Sodium Azide; Constituents: 1% BSA 10mM Sodium Phosphate

Plasma membrane Fibroblast growth factors (FGFs) are members of a large family of structurally related polypeptides (MW 17-38 kD) that are potent physiological regulators of growth and differentiation for a wide variety of cells of mesodermal ectodermal and endodermal origin. FGFs are substantially involved in normal development wound healing and repair angiogenesis a variety of neurotrophic activities and in hematopoiesis as well as in tissue remodelling and maintenance. They have also been implicated in pathological conditions such as tumorigenesis and metastasis. The FGF family consists of at least seventeen members designated FGF1 through FGF17. To date four genes encoding for high affinity cell surface FGF receptors (FGFRs) have been identified: FGFR1 [flg-1(fms-like gene 1)]; FGFR2 [bek (bacterial expressed kinase gene product)]; FGFR3 (cek-2) and by alternative splicing have been reported. Soluble secreted or possibly cleaved forms of FGFR-1 and FGFR-2 have also been found in body fluids or were artificially constructed. An example is a soluble FGF-binding protein containing the extracellular region of FGFR3 and the secreted form of placental alkaline phosphatase (FRAP3). FGFRs are members of the tyrosine kinase family of growth factor receptors. They are glycosylated 110-150 kD proteins consiting of an extracellular domain a single transmembrane region and a cytoplasmic split tyrosine kinase domain which is activated following ligand binding and receptor dimerization. The extracellular ligand binding region is constructed with either two (beta type) or typically three (alpha-type) immunoglobulin (Ig)-like domains and an eight amino acid ë acidic boxí . The ligand binding site of all FGFRs is confined to the extracellular Ig-like domains 2 and 3. FGFRs exhibit overlapping recognition and redundant specificity. One receptor type may bind several of the FGFs with a similar affinity. Also one FGF type may bind similarly to several distinct receptors. This accounts for the rather identical effects of different FGF ligands on common cell types. FGFs binding to cellular FGFRs depend on or is markedly facilitated by the low-affinity interaction of FGFs with the polysaccharide component of cell surface or extracellular matrix heparan sulfate proteoglycans (HSPG). Signal transduction by FGFRs requires dimerization or oligomerization and autophosphorylation of the receptors through their tyrosine kinase domain. Subsequent association with cytoplasmic signalling molecules leads to DNA synthesis or differentiation. The signalling and biological responses elicited by distinct FGFRs substantially differ and are dictated by the intracellular domain. FGFR3 is widely expressed in many fetal and adult human and animal tissues. The FGFR3 expression profile largely correlates with its tissue specific expression at the mRNA level.

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Expressed in brain kidney and testis. Very low or no expression in spleen heart and muscle. In 20- to 22-week old fetuses it is expressed at high level in kidney lung small intestine and brain and to a lower degree in spleen liver and muscle. Epithelial cells show exclusively isoform 2 transcripts while fibroblastic cells show a mixture of isoform 1 and isoform 2.

Defects in FGFR3 are the cause of Crouzon syndrome with acanthosis nigricans (CAN) [MIM:612247]. Classic Crouzon disease which is caused by mutations in the FGFR2 gene is characterized by craniosynostosis (premature fusion of the skull sutures) and facial hypoplasia. Crouzon syndrome with acanthosis nigricans (a skin disorder characterized by pigmentation anomalies) CAN is considered to be an independant disorder from classic Crouzon syndrome. CAN is characterized by additional more severe physical manifestation such as Chiari malformation hydrocephalus and atresia or stenosis of the choanas and is caused by a specific mutation (Ala-391 to Glu) in the transmembrane domain of FGFR3. It is proposed to have an autosonal dominant mode of inheritance.

Defects in FGFR3 are a cause of thanatophoric dysplasia (TD) [MIM:187600 187601]; also known as thanatophoric dwarfism. TD is the most common neonatal lethal skeletal dysplasia. Affected individuals display features similar to those seen in homozygous achondroplasia. It causes severe shortening of the limbs with macrocephaly narrow thorax and short ribs. In the most common subtype TD1 femur are curved while in TD2 straight femurs are associated with cloverleaf skull. Mutations affecting different functional domains of FGFR3 cause different forms of this lethal disorder.

Defects in FGFR3 are a cause of bladder cancer [MIM:109800]. Somatic mutations can constitutively activate FGFR3.

Defects in FGFR3 are the cause of camptodactyly tall stature and hearing loss syndrome (CATSHL syndrome) [MIM:610474]. CATSHL syndrome is an autosomal dominant syndrome characterized by permanent and irreducible flexion of one or more fingers of the hand and/or feet tall stature scoliosis and/or a pectus excavatum and hearing loss. Affected individuals have developmental delay and/or mental retardation and several of these have microcephaly. Radiographic findings included tall vertebral bodies with irregular borders and broad femoral metaphyses with long tubular shafts. On audiological exam each tested member have bilateral sensorineural hearing loss and absent otoacoustic emissions. The hearing loss was congenital or developed in early infancy progressed variably in early childhood and range from mild to severe. Computed tomography and magnetic resonance imaging reveal that the brain middle ear and inner ear are structurally normal.

Defects in FGFR3 are a cause of lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:149730]; also known as Levy-Hollister syndrome. LADDS is a form of ectodermal dysplasia a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. LADDS is an autosomal dominant syndrome characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts cup-shaped ears hearing loss hypodontia and enamel hypoplasia and distal limb segments anomalies. In addition to these cardinal features facial dysmorphism malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed.

Defects in FGFR3 are a cause of Muenke syndrome (MNKS) [MIM:602849]; also known as Muenke non-syndromic coronal craniosynostosis. MNKS is a condition characterized by premature closure of coronal suture of skull during development (coronal craniosynostosis) which affects the shape of the head and face. It may be uni- or bilateral. When bilateral it is characterized by a skull with a small antero-posterior diameter (brachycephaly) often with a decrease in the depth of the orbits and hypoplasia of the maxillae. Unilateral closure of the coronal sutures leads to flattening of the orbit on the involved side (plagiocephaly). The intellect is normal. In addition to coronal craniosynostosis some affected individuals show skeletal abnormalities of hands and feet sensorineural hearing loss mental retardation and respiratory insufficiency. Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily. Similarity: Contains 3 Ig-like C2-type (immunoglobulin-like) domains. Similarity: Contains 1 protein kinase domain.