Fibroblast growth factor receptor 1

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Fibroblast growth factor receptor 1
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols FGFR1 ; BFGFR; CD331; CEK; FGFBR; FGFR-1; FLG; FLT-2; FLT2; HBGFR; HH2; KAL2; N-SAM; OGD; bFGF-R-1
External IDs OMIM136350 MGI95522 HomoloGene69065 ChEMBL: 3650 GeneCards: FGFR1 Gene
EC number 2.7.10.1
RNA expression pattern
PBB GE FGFR1 211535 s at tn.png
PBB GE FGFR1 207937 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2260 14182
Ensembl ENSG00000077782 ENSMUSG00000031565
UniProt P11362 P16092
RefSeq (mRNA) NM_001174063 NM_001079908
RefSeq (protein) NP_001167534 NP_001073377
Location (UCSC) Chr 8:
38.27 – 38.33 Mb
Chr 8:
25.51 – 25.58 Mb
PubMed search [1] [2]

Fibroblast growth factor receptor 1 (FGFR1), also known as basic fibroblast growth factor receptor 1, fms-related tyrosine kinase-2 / Pfeiffer syndrome, and CD331, is a receptor tyrosine kinase whose ligands are specific members of the fibroblast growth factor family. FGFR1 has been shown to be associated with Pfeiffer syndrome.[1]

Function[edit]

The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) 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 consists 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, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction.

Clinical significance[edit]

Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, squamous cell lung cancer (14) and autosomal dominant Kallmann syndrome. There is also strong evidence from sequencing studies of candidate genes involved in clefting that mutations in the FGFR1 gene may be associated in the pathogenesis of cleft lip and/or palate.[2] A few DNA sequence variants, including one nonsense mutation, have been reported in isolated or non-syndromic cleft lip and palate.[3] Both cleft lip with or without a cleft palate and cleft palate only features have been seen in families with a FGFRI mutation.[2] Cleft palate is a relatively common feature of Kallman syndrome as well.[2][4][5] Somatic chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.[6]

Mutations in in this gene have been associated to Hartsfield syndrome .[7]

Interactions[edit]

Fibroblast growth factor receptor 1 has been shown to interact with GRB14,[8] SHB,[9] FRS2,[10][11][12][13] Klotho,[14] and FGF1.[15][16]

See also[edit]

References[edit]

  1. ^ Itoh N, Terachi T, Ohta M, Seo MK (June 1990). "The complete amino acid sequence of the shorter form of human basic fibroblast growth factor receptor deduced from its cDNA". Biochem. Biophys. Res. Commun. 169 (2): 680–5. doi:10.1016/0006-291X(90)90384-Y. PMID 2162671. 
  2. ^ a b c Dixon MJ, Marazita ML, Beaty TH, Murray JC (March 2011). "Cleft lip and palate: understanding genetic and environmental influences". Nat. Rev. Genet. 12 (3): 167–78. doi:10.1038/nrg2933. PMC 3086810. PMID 21331089. 
  3. ^ Riley BM, Mansilla MA, Ma J, Daack-Hirsch S, Maher BS, Raffensperger LM, Russo ET, Vieira AR, Dodé C, Mohammadi M, Marazita ML, Murray JC (March 2007). "Impaired FGF signaling contributes to cleft lip and palate". Proc. Natl. Acad. Sci. U.S.A. 104 (11): 4512–7. doi:10.1073/pnas.0607956104. PMC 1810508. PMID 17360555. 
  4. ^ Kim HG, Herrick SR, Lemyre E, Kishikawa S, Salisz JA, Seminara S, MacDonald ME, Bruns GA, Morton CC, Quade BJ, Gusella JF (August 2005). "Hypogonadotropic hypogonadism and cleft lip and palate caused by a balanced translocation producing haploinsufficiency for FGFR1". J. Med. Genet. 42 (8): 666–72. doi:10.1136/jmg.2004.026989. PMC 1736121. PMID 16061567. 
  5. ^ Dodé C, Fouveaut C, Mortier G, Janssens S, Bertherat J, Mahoudeau J, Kottler ML, Chabrolle C, Gancel A, François I, Devriendt K, Wolczynski S, Pugeat M, Pineiro-Garcia A, Murat A, Bouchard P, Young J, Delpech M, Hardelin JP (January 2007). "Novel FGFR1 sequence variants in Kallmann syndrome, and genetic evidence that the FGFR1c isoform is required in olfactory bulb and palate morphogenesis". Hum. Mutat. 28 (1): 97–8. doi:10.1002/humu.9470. PMID 17154279. 
  6. ^ "Entrez Gene: FGFR1 fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, Pfeiffer syndrome)". 
  7. ^ Dhamija, R; Kirmani, S; Wang, X; Ferber, M. J.; Wieben, E. D.; Lazaridis, K. N.; Babovic-Vuksanovic, D (2014). "Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield syndrome: A case of gonadal mosaicism". American Journal of Medical Genetics Part A: n/a. doi:10.1002/ajmg.a.36621. PMID 24888332.  edit
  8. ^ Reilly JF, Mickey G, Maher PA (March 2000). "Association of fibroblast growth factor receptor 1 with the adaptor protein Grb14. Characterization of a new receptor binding partner". J. Biol. Chem. 275 (11): 7771–8. doi:10.1074/jbc.275.11.7771. PMID 10713090. 
  9. ^ Karlsson T, Songyang Z, Landgren E, Lavergne C, Di Fiore PP, Anafi M, Pawson T, Cantley LC, Claesson-Welsh L, Welsh M (April 1995). "Molecular interactions of the Src homology 2 domain protein Shb with phosphotyrosine residues, tyrosine kinase receptors and Src homology 3 domain proteins". Oncogene 10 (8): 1475–83. PMID 7537362. 
  10. ^ Yan KS, Kuti M, Yan S, Mujtaba S, Farooq A, Goldfarb MP, Zhou MM (May 2002). "FRS2 PTB domain conformation regulates interactions with divergent neurotrophic receptors". J. Biol. Chem. 277 (19): 17088–94. doi:10.1074/jbc.M107963200. PMID 11877385. 
  11. ^ Ong SH, Guy GR, Hadari YR, Laks S, Gotoh N, Schlessinger J, Lax I (February 2000). "FRS2 Proteins Recruit Intracellular Signaling Pathways by Binding to Diverse Targets on Fibroblast Growth Factor and Nerve Growth Factor Receptors". Mol. Cell. Biol. 20 (3): 979–89. doi:10.1128/MCB.20.3.979-989.2000. PMC 85215. PMID 10629055. 
  12. ^ Xu H, Lee KW, Goldfarb M (July 1998). "Novel recognition motif on fibroblast growth factor receptor mediates direct association and activation of SNT adapter proteins". J. Biol. Chem. 273 (29): 17987–90. doi:10.1074/jbc.273.29.17987. PMID 9660748. 
  13. ^ Dhalluin C, Yan KS, Plotnikova O, Lee KW, Zeng L, Kuti M, Mujtaba S, Goldfarb MP, Zhou MM (October 2000). "Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors". Mol. Cell 6 (4): 921–9. doi:10.1016/S1097-2765(05)00087-0. PMID 11090629. 
  14. ^ Urakawa I, Jamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yameshita T (October 2006). "Klotho converts canonical FGF receptor into a specific receptor for FGF23". Nature. 444: 770–4. doi:10.1038/nature05315. PMID 7086194. 
  15. ^ Schlessinger J, Plotnikov AN, Ibrahimi OA, Eliseenkova AV, Yeh BK, Yayon A, Linhardt RJ, Mohammadi M (September 2000). "Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization". Mol. Cell 6 (3): 743–50. doi:10.1016/S1097-2765(00)00073-3. PMID 11030354. 
  16. ^ Santos-Ocampo S, Colvin JS, Chellaiah A, Ornitz DM (January 1996). "Expression and biological activity of mouse fibroblast growth factor-9". J. Biol. Chem. 271 (3): 1726–31. doi:10.1074/jbc.271.3.1726. PMID 8576175. 

Further reading[edit]

  • Weiss J, Sos ML, Seidel D et al. (December 2010). "Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer". Sci Transl Med 2 (62): 62ra93. doi:10.1126/scitranslmed.3001451. PMID 21160078. 
  • Johnson DE, Williams LT (1993). "Structural and functional diversity in the FGF receptor multigene family". Adv. Cancer Res. Advances in Cancer Research 60: 1–41. doi:10.1016/S0065-230X(08)60821-0. ISBN 978-0-12-006660-5. PMID 8417497. 
  • Macdonald D, Reiter A, Cross NC (2002). "The 8p11 myeloproliferative syndrome: a distinct clinical entity caused by constitutive activation of FGFR1". Acta Haematol. 107 (2): 101–7. doi:10.1159/000046639. PMID 11919391. 
  • Groth C, Lardelli M (2003). "The structure and function of vertebrate fibroblast growth factor receptor 1". Int. J. Dev. Biol. 46 (4): 393–400. PMID 12141425. 
  • Wilkie AO (2005). "Bad bones, absent smell, selfish testes: the pleiotropic consequences of human FGF receptor mutations". Cytokine Growth Factor Rev. 16 (2): 187–203. doi:10.1016/j.cytogfr.2005.03.001. PMID 15863034. 

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.