Fibroblast growth factor receptor 3

FGFR-3 is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals which ultimately influence cell mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factor and plays a role in bone development and maintenance. The FGFR-3 protein plays a role in bone growth by regulating ossification. == Mutations ==

Simplification on the mutation 46 XX 4q16.3 (female), 46XY 4q16.3 (male). Gain of function mutations in this gene can develop dysfunctional proteins "impede cartilage growth and development and affect chondrocyte proliferation and calcification" This point mutation in the FGFR3 gene causes hydrogen bonds to form between two arginine side chains leading to ligand-independent stabilization of FGFR3 dimers. Overactivity of FGFR3 inhibits chondrocyte proliferation and restricts long bone length. ==Disease linkage==

Defects in the FGFR3 gene has been associated with several conditions, including craniosynostosis and seborrheic keratosis. Bladder cancer Mutations of FGFR3, FGFR3–TACC3 and FGFR3–BAIAP2L1 fusion proteins are frequently associated with bladder cancer, while some FGFR3 mutations are also associated with a better prognosis. Hence FGFR3 represents a potential therapeutic target for the treatment of bladder cancer. Post-translational modification of FGFR3 occur in bladder cancer that do not occur in normal cells and can be targeted by immunotherapeutic antibodies. Glioblastoma FGFR3-TACC3 fusions have been identified as the primary mitogenic drivers in a subset of glioblastomas (approximately 4%) and other gliomas and may be associated with slightly improved overall survival. The FGFR3-TACC3 fusion represents a possible therapeutic target in glioblastoma. Achondroplasia Achondroplasia is a dominant genetic disorder caused by mutations in FGFR3 that make the resulting protein overactive. Individuals with these mutation have a head size that is larger than normal and are significantly shorter in height. Only a single copy of the mutated FGFR3 gene results in achondroplasia. Thanatophoric dysplasia Thanatophoric dysplasia is a genetic disorder caused by mutations in FGFR3 that is often fatal. There are two types. TD type I is caused by a premature stop codon mutation. Characteristics of Muenke syndrome include coronal synostosis (usually bilateral), midfacial retrusion, strabismus, hearing loss, and developmental delay. Turribrachycephaly, cloverleaf skull, and frontal bossing are also possible. ==As a drug target==

An FGFR3 inhibitor known as erdafitinib has been approved as a cancer treatment in several jurisdictions for FGFR3+ urothelial carcinoma. The FGFR3 receptor has a tyrosine kinase signaling pathway that is associated with many biological developments embryonically and in tissues. Studying the tyrosine kinase signaling pathway that FGFR3 displays has played a crucial role in the development of research of several cell activities such as cell proliferation and cellular resistance to anti-cancer medications. == Interactions ==

Fibroblast growth factor receptor 3 has been shown to interact with FGF8 and FGF9. == See also ==