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
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
Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. A few variants, including one nonsense mutation, have also been reported in isolated or non-syndromic cleft lip and palate.[2] Clefts are a relatively common featrue of Kallman syndrome as well.[3][4] 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.[5]
Interactions
Fibroblast growth factor receptor 1 has been shown to interact with GRB14,[6] SHB,[7] FRS2[8][9][10][11] and FGF1.[12][13]
See also
References
- ^ 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.
- ^ 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. PMID 17360555.
- ^ 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. PMID 16061567.
- ^ 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.
- ^ "Entrez Gene: FGFR1 fibroblast growth factor receptor 1 (fms-related tyrosine kinase 2, Pfeiffer syndrome)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2260.
- ^ Reilly, J F; Mickey G, Maher P A (Mar. 2000). "Association of fibroblast growth factor receptor 1 with the adaptor protein Grb14. Characterization of a new receptor binding partner". J. Biol. Chem. (UNITED STATES) 275 (11): 7771–8. ISSN 0021-9258. PMID 10713090.
- ^ Karlsson, T; Songyang Z, Landgren E, Lavergne C, Di Fiore P P, Anafi M, Pawson T, Cantley L C, Claesson-Welsh L, Welsh M (Apr. 1995). "Molecular interactions of the Src homology 2 domain protein Shb with phosphotyrosine residues, tyrosine kinase receptors and Src homology 3 domain proteins". Oncogene (ENGLAND) 10 (8): 1475–83. ISSN 0950-9232. PMID 7537362.
- ^ Yan, Kelley S; Kuti Miklos, Yan Sherry, Mujtaba Shiraz, Farooq Amjad, Goldfarb Mitchell P, Zhou Ming-Ming (May. 2002). "FRS2 PTB domain conformation regulates interactions with divergent neurotrophic receptors". J. Biol. Chem. (United States) 277 (19): 17088–94. doi:10.1074/jbc.M107963200. ISSN 0021-9258. PMID 11877385.
- ^ Ong, S H; Guy G R, Hadari Y R, Laks S, Gotoh N, Schlessinger J, Lax I (Feb. 2000). "FRS2 proteins recruit intracellular signaling pathways by binding to diverse targets on fibroblast growth factor and nerve growth factor receptors". Mol. Cell. Biol. (UNITED STATES) 20 (3): 979–89. ISSN 0270-7306. PMID 10629055.
- ^ Xu, H; Lee K W, Goldfarb M (Jul. 1998). "Novel recognition motif on fibroblast growth factor receptor mediates direct association and activation of SNT adapter proteins". J. Biol. Chem. (UNITED STATES) 273 (29): 17987–90. ISSN 0021-9258. PMID 9660748.
- ^ Dhalluin, C; Yan K S, Plotnikova O, Lee K W, Zeng L, Kuti M, Mujtaba S, Goldfarb M P, Zhou M M (Oct. 2000). "Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors". Mol. Cell (United States) 6 (4): 921–9. ISSN 1097-2765. PMID 11090629.
- ^ Schlessinger, J; Plotnikov A N, Ibrahimi O A, Eliseenkova A V, Yeh B K, Yayon A, Linhardt R J, Mohammadi M (Sep. 2000). "Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization". Mol. Cell (UNITED STATES) 6 (3): 743–50. ISSN 1097-2765. PMID 11030354.
- ^ Santos-Ocampo, S; Colvin J S, Chellaiah A, Ornitz D M (Jan. 1996). "Expression and biological activity of mouse fibroblast growth factor-9". J. Biol. Chem. (UNITED STATES) 271 (3): 1726–31. ISSN 0021-9258. PMID 8576175.
Further reading
- Johnson DE, Williams LT (1993). "Structural and functional diversity in the FGF receptor multigene family.". Adv. Cancer Res. 60: 1–41. doi:10.1016/S0065-230X(08)60821-0. 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.
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1agw: CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FIBROBLAST GROWTH FACTOR RECEPTOR 1 IN COMPLEX WITH SU4984 INHIBITOR
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1cvs: CRYSTAL STRUCTURE OF A DIMERIC FGF2-FGFR1 COMPLEX
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1evt: CRYSTAL STRUCTURE OF FGF1 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 1 (FGFR1)
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1fgi: CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FIBROBLAST GROWTH FACTOR RECEPTOR 1 IN COMPLEX WITH SU5402 INHIBITOR
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1fgk: CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FIBROBLAST GROWTH FACTOR RECEPTOR 1
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1fq9: CRYSTAL STRUCTURE OF A TERNARY FGF2-FGFR1-HEPARIN COMPLEX
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2ckn: NMR STRUCTURE OF THE FIRST IG MODULE OF MOUSE FGFR1
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2cr3: Solution structure of the first Ig-like domain of human fibroblast growth factor receptor 1
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2fgi: CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FGF RECEPTOR 1 IN COMPLEX WITH INHIBITOR PD173074
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External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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Proteins: clusters of differentiation (see also list of human clusters of differentiation) |
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| 1-50 |
CD1 ( a-c, 1A, 1D, 1E) · CD2 · CD3 ( γ, δ, ε) · CD4 · CD5 · CD6 · CD7 · CD8 ( a) · CD9 · CD10 · CD11 ( a, b, c) · CD13 · CD14 · CD15 · CD16 ( A, B) · CD18 · CD19 · CD20 · CD21 · CD22 · CD23 · CD24 · CD25 · CD26 · CD27 · CD28 · CD29 · CD30 · CD31 · CD32 ( A, B) · CD33 · CD34 · CD35 · CD36 · CD37 · CD38 · CD39 · CD40 · CD41 · CD42 ( a, b, c, d) · CD43 · CD44 · CD45 · CD46 · CD47 · CD48 · CD49 ( a, b, c, d, e, f) · CD50
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| 51-100 |
CD51 · CD52 · CD53 · CD54 · CD55 · CD56 · CD57 · CD58 · CD59 · CD61 · CD62 ( E, L, P) · CD63 · CD64 ( A, B, C) · CD66 ( a, b, c, d, e, f) · CD68 · CD69 · CD70 · CD71 · CD72 · CD73 · CD74 · CD78 · CD79 ( a, b) · CD80 · CD81 · CD82 · CD83 · CD84 · CD85 ( a, d, e, h, j, k) · CD86 · CD87 · CD88 · CD89 · CD90 · CD91- CD92 · CD93 · CD94 · CD95 · CD97 · CD98 · CD99 · CD100
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| 101-150 |
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| 151-200 |
CD151 · CD152 · CD153 · CD154 · CD155 · CD156 ( a, b, c) · CD157 · CD158 ( a, d, e, i, k) · CD159 ( a, c) · CD160 · CD161 · CD162 · CD163 · CD164 · CD166 · CD167 ( a, b) · CD168 · CD169 · CD170 · CD171 · CD172 ( a, b, g) · CD174 · CD177 · CD178 · CD179 ( a, b) · CD181 · CD182 · CD183 · CD184 · CD185 · CD186 · CD191 · CD192 · CD193 · CD194 · CD195 · CD196 · CD197 · CDw198 · CDw199 · CD200
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| 201-250 |
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| 251-300 |
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| 301-350 |
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