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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/09/27 12:03:00」(JST)

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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, 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

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]

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.
^ ^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.
^ 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.
^ 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.
^ 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)".
^ 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
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

External links

GeneReviews/NIH/NCBI/UW entry on FGFR-Related Craniosynostosis Syndromes
GeneReviews/NCBI/NIH/UW entry on Kallmann syndrome
FGFR1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
Fibroblast growth factor receptor 1 on the Atlas of Genetics and Oncology
FGFR1 human gene location in the UCSC Genome Browser.
FGFR1 human gene details in the UCSC Genome Browser.

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

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「線維芽細胞増殖因子受容体1」

Fibroblast growth factor receptor 1
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1AGW, 1CVS, 1EVT, 1FGI, 1FGK, 1FQ9, 1XR0, 2CR3, 2FGI, 3C4F, 3DPK, 3GQI, 3GQL, 3JS2, 3KRJ, 3KRL, 3KXX, 3KY2, 3OJV, 3RHX, 3TT0, 4F63, 4F64, 4F65, 4NK9, 4NKA, 4NKS
Identifiers
Symbols	FGFR1 ; BFGFR; CD331; CEK; FGFBR; FGFR-1; FLG; FLT-2; FLT2; HBGFR; HH2; HRTFDS; KAL2; N-SAM; OGD; bFGF-R-1
External IDs	OMIM: 136350 MGI: 95522 HomoloGene: 69065 ChEMBL: 3650 GeneCards: FGFR1 Gene
EC number	2.7.10.1
Gene ontology
Molecular function	• protein tyrosine kinase activity; • fibroblast growth factor-activated receptor activity; • protein binding; • ATP binding; • heparin binding; • fibroblast growth factor binding; • identical protein binding; • protein homodimerization activity;
Cellular component	• extracellular region; • nucleus; • cytosol; • plasma membrane; • integral component of plasma membrane; • integral component of membrane; • cytoplasmic membrane-bounded vesicle; • receptor complex;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • MAPK cascade; • skeletal system development; • angiogenesis; • ureteric bud development; • in utero embryonic development; • organ induction; • neuron migration; • positive regulation of mesenchymal cell proliferation; • chondrocyte differentiation; • transcription, DNA-templated; • protein phosphorylation; • epidermal growth factor receptor signaling pathway; • axon guidance; • sensory perception of sound; • positive regulation of cell proliferation; • insulin receptor signaling pathway; • fibroblast growth factor receptor signaling pathway; • positive regulation of phospholipase activity; • positive regulation of phospholipase C activity; • positive regulation of neuron projection development; • positive regulation of phosphatidylinositol 3-kinase signaling; • cell migration; • peptidyl-tyrosine phosphorylation; • ventricular zone neuroblast division; • embryonic limb morphogenesis; • midbrain development; • fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development; • Fc-epsilon receptor signaling pathway; • inner ear morphogenesis; • outer ear morphogenesis; • middle ear morphogenesis; • chordate embryonic development; • positive regulation of MAP kinase activity; • positive regulation of MAPK cascade; • innate immune response; • regulation of cell differentiation; • positive regulation of neuron differentiation; • positive regulation of cell cycle; • protein autophosphorylation; • neurotrophin TRK receptor signaling pathway; • phosphatidylinositol-mediated signaling; • paraxial mesoderm development; • regulation of lateral mesodermal cell fate specification; • cell maturation; • skeletal system morphogenesis; • mesenchymal cell differentiation; • positive regulation of cardiac muscle cell proliferation; • auditory receptor cell development; • branching involved in salivary gland morphogenesis; • lung-associated mesenchyme development; • regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling; • positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway; • regulation of extrinsic apoptotic signaling pathway in absence of ligand;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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