Fibroblast growth factor receptor

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Contents

Function

Fibroblast growth factor receptors (FGFR) are receptors which bind fibroblast growth factors (FGF). Each FGFR can activate several FGFs. Five FGFRs have been identified so far. FGFRs differ in their ligand specificity and tissue distribution. The binding of FGF to FGFR starts a cascade of signaling which influences mitogenesis and differentiation[1]. See also Receptor tyrosine kinases and Kinase-linked, enzyme-linked and related receptors.

  • FGFR2 is essential for limb induction[2].
  • FGFR3 is involved in skeletal dysplasia[3].

Disease

Mutation in FGFR3 causes achondroplasia[4] and is involved in myeloma[5]. Mutations in FGFR2 cause Crouzon syndrome[6].

Structural insights

FGFR consist of an extracellular ligand-binding domain (LBD), transmembrane helix domain and cytoplasmic tyrosine kinase activity domain (TKD) with phosphorylated tyrosine designated PTR. FGFR LBD contains 3 immunoglobulin-like domains D1, D2 and D3.

Human fibroblast growth factor receptor 1 ligand-binding domain modules D2 and D3 with 2 molecules of fibroblast growth factor 1 (PDB code 1evt).

3D structures of fibroblast growth factor receptor

Fibroblast growth factor receptor 3D receptor


Human fibroblast growth factor receptor 1 ligand-binding domain modules D2 and D3 (pink and yellow) complex with fibroblast growth factor 1 (cyan and green) and sulfate (PDB code 1evt)

Drag the structure with the mouse to rotate

References

  1. Coutts JC, Gallagher JT. Receptors for fibroblast growth factors. Immunol Cell Biol. 1995 Dec;73(6):584-9. PMID:8713482 doi:http://dx.doi.org/10.1038/icb.1995.92
  2. Xu X, Weinstein M, Li C, Naski M, Cohen RI, Ornitz DM, Leder P, Deng C. Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development. 1998 Feb;125(4):753-65. PMID:9435295 doi:10.1242/dev.125.4.753
  3. Foldynova-Trantirkova S, Wilcox WR, Krejci P. Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias. Hum Mutat. 2012 Jan;33(1):29-41. PMID:22045636 doi:10.1002/humu.21636
  4. Wilkin DJ, Szabo JK, Cameron R, Henderson S, Bellus GA, Mack ML, Kaitila I, Loughlin J, Munnich A, Sykes B, Bonaventure J, Francomano CA. Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. Am J Hum Genet. 1998 Sep;63(3):711-6. PMID:9718331 doi:http://dx.doi.org/10.1086/302000
  5. Intini D, Baldini L, Fabris S, Lombardi L, Ciceri G, Maiolo AT, Neri A. Analysis of FGFR3 gene mutations in multiple myeloma patients with t(4;14). Br J Haematol. 2001 Aug;114(2):362-4. PMID:11529856
  6. Meyers GA, Orlow SJ, Munro IR, Przylepa KA, Jabs EW. Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. Nat Genet. 1995 Dec;11(4):462-4. PMID:7493034 doi:http://dx.doi.org/10.1038/ng1295-462

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