Fibroblast growth factor receptor 3 is a protein that in humans is encoded by the FGFR3gene.[1] FGFR3 has also been designated as CD333 (cluster of differentiation 333). The gene, which is located on chromosome 4, location p16.3, is "expressed in tissues such as the cartilage, brain, intestine, and kidneys."[2]
The protein encoded by this gene 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 influencing 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. Alternative splicing occurs and additional variants have been described, including those utilizing alternate exon 8 rather than 9, but their full-length nature has not been determined.[3]
Mutations
Mutations in this gene can develop dysfunctional proteins "impede cartilage growth and development and affect chondrocyte proliferation and calcification"[2] which can lead to craniosynostosis and multiple types of skeletal dysplasia (Osteochondrodysplasia). The point mutation in the FGFR3 gene causes hydrogen bonds to form between two arginine side chains leading to ligand-independent stabilization FGFR3 dimers. Point mutations in the FGFR3 gene, "causes defective growth of long tubular bones".[4] By inhibiting chondrocyte proliferation, FGFR3 restricts long bone length.[5] In achondroplasia, the FGFR3 gene has a point mutation at nucleotide 1138 resulting from either a G>A or G>C.[5] FGFR3 mutations are linked with spermatocytic seminoma, which occur more frequently in older men.[4]
Disease linkage
Defects in the FGFR3 gene has been associated with several conditions, including:
↑ 2.02.1Wang, Y., Liu, Z., Liu, Z., Zhao, H., Zhou, X., Cui, Y., & Han, J. (2013). Advances in research on and diagnosis and treatment of achondroplasia in China. Intractable & Rare Diseases Research, 2(2), 45-50.
↑Hafner C, Hartmann A, Vogt T (July 2007). "FGFR3 mutations in epidermal nevi and seborrheic keratoses: lessons from urothelium and skin". The Journal of Investigative Dermatology. 127 (7): 1572–3. doi:10.1038/sj.jid.5700772. PMID17568799.
↑Lamy A, Gobet F, Laurent M, Blanchard F, Varin C, Moulin C, Andreou A, Frebourg T, Pfister C (December 2006). "Molecular profiling of bladder tumors based on the detection of FGFR3 and TP53 mutations". The Journal of Urology. 176 (6 Pt 1): 2686–9. doi:10.1016/j.juro.2006.07.132. PMID17085196.
↑Mulliken JB, Steinberger D, Kunze S, Müller U (November 1999). "Molecular diagnosis of bilateral coronal synostosis". Plastic and Reconstructive Surgery. 104 (6): 1603–15. doi:10.1097/00006534-199911000-00001. PMID10541159.
↑ 9.09.1Santos-Ocampo S, Colvin JS, Chellaiah A, Ornitz DM (January 1996). "Expression and biological activity of mouse fibroblast growth factor-9". The Journal of Biological Chemistry. 271 (3): 1726–31. doi:10.1074/jbc.271.3.1726. PMID8576175.
↑ 10.010.1Chellaiah A, Yuan W, Chellaiah M, Ornitz DM (December 1999). "Mapping ligand binding domains in chimeric fibroblast growth factor receptor molecules. Multiple regions determine ligand binding specificity". The Journal of Biological Chemistry. 274 (49): 34785–94. doi:10.1074/jbc.274.49.34785. PMID10574949.
Further reading
Schweitzer DN, Graham JM, Lachman RS, Jabs EW, Okajima K, Przylepa KA, Shanske A, Chen K, Neidich JA, Wilcox WR (January 2001). "Subtle radiographic findings of achondroplasia in patients with Crouzon syndrome with acanthosis nigricans due to an Ala391Glu substitution in FGFR3". American Journal of Medical Genetics. 98 (1): 75–91. doi:10.1002/1096-8628(20010101)98:1<75::AID-AJMG1010>3.0.CO;2-6. PMID11426459.
Horton WA, Lunstrum GP (December 2002). "Fibroblast growth factor receptor 3 mutations in achondroplasia and related forms of dwarfism". Reviews in Endocrine & Metabolic Disorders. 3 (4): 381–5. PMID12424440.
Bonaventure J, Silve C (November 2005). "[Hereditary skeletal dysplasias and FGFR3 and PTHR1 signaling pathways]". Médecine Sciences. 21 (11): 954–61. doi:10.1051/medsci/20052111954. PMID16274647.
Hernández S, Toll A, Baselga E, Ribé A, Azua-Romeo J, Pujol RM, Real FX (July 2007). "Fibroblast growth factor receptor 3 mutations in epidermal nevi and associated low grade bladder tumors". The Journal of Investigative Dermatology. 127 (7): 1664–6. doi:10.1038/sj.jid.5700705. PMID17255960.
