Fibroblast growth factor receptor 1

NameFibroblast growth factor receptor 1
Synonyms
  • 2.7.10.1
  • Basic fibroblast growth factor receptor 1
  • bFGF-R-1
  • BFGFR
  • CEK
  • FGFBR
  • FGFR-1
  • FLG
  • FLT-2
  • FLT2
  • Fms-like tyrosine kinase 2
  • HBGFR
  • N-sam
  • Proto-oncogene c-Fgr
Gene NameFGFR1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0004180|Fibroblast growth factor receptor 1
MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRLRDD
VQSINWLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYFSVNVSD
ALPSSEDDDDDDDSSSEEKETDNTKPNRMPVAPYWTSPEKMEKKLHAVPAAKTVKFKCPS
SGTPNPTLRWLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNYTCIVENEYGSIN
HTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQPHIQWLKHIEVNGSKI
GPDNLPYVQILKTAGVNTTDKEMEVLHLRNVSFEDAGEYTCLAGNSIGLSHHSAWLTVLE
ALEERPAVMTSPLYLEIIIYCTGAFLISCMVGSVIVYKMKSGTKKSDFHSQMAVHKLAKS
IPLRRQVTVSADSSASMNSGVLLVRPSRLSSSGTPMLAGVSEYELPEDPRWELPRDRLVL
GKPLGEGCFGQVVLAEAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIGK
HKNIINLLGACTQDGPLYVIVEYASKGNLREYLQARRPPGLEYCYNPSHNPEEQLSSKDL
VSCAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYKKTTNG
RLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMD
KPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIVALTSNQEYLDLSMPLDQYSPSF
PDTRSSTCSSGEDSVFSHEPLPEEPCLPRHPAQLANGGLKRR
Number of residues822
Molecular Weight91866.935
Theoretical pI6.14
GO Classification
Functions
  • protein homodimerization activity
  • protein tyrosine kinase activity
  • heparin binding
  • ATP binding
  • identical protein binding
  • fibroblast growth factor-activated receptor activity
  • fibroblast growth factor binding
Processes
  • activation of MAPKK activity
  • lung-associated mesenchyme development
  • regulation of cell differentiation
  • positive regulation of phospholipase C activity
  • middle ear morphogenesis
  • fibroblast growth factor receptor signaling pathway
  • protein autophosphorylation
  • positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway
  • insulin receptor signaling pathway
  • mesenchymal cell differentiation
  • in utero embryonic development
  • skeletal system morphogenesis
  • chordate embryonic development
  • auditory receptor cell development
  • MAPK cascade
  • midbrain development
  • positive regulation of neuron differentiation
  • motogenic signaling involved in postnatal olfactory bulb interneuron migration
  • neurotrophin TRK receptor signaling pathway
  • positive regulation of cardiac muscle cell proliferation
  • transcription, DNA-templated
  • outer ear morphogenesis
  • protein phosphorylation
  • positive regulation of cell cycle
  • cell maturation
  • paraxial mesoderm development
  • Ras protein signal transduction
  • positive regulation of mesenchymal cell proliferation
  • axon guidance
  • stem cell population maintenance
  • regulation of extrinsic apoptotic signaling pathway in absence of ligand
  • vascular endothelial growth factor receptor signaling pathway
  • positive regulation of phospholipase activity
  • cell migration
  • regulation of sensory perception of pain
  • positive regulation of cell proliferation
  • ureteric bud development
  • epidermal growth factor receptor signaling pathway
  • positive regulation of MAPK cascade
  • positive regulation of phosphatidylinositol 3-kinase signaling
  • ventricular zone neuroblast division
  • innate immune response
  • peptidyl-tyrosine phosphorylation
  • positive regulation of neuron projection development
  • negative regulation of transcription from RNA polymerase II promoter
  • chondrocyte differentiation
  • neuron migration
  • angiogenesis
  • regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling
  • Fc-epsilon receptor signaling pathway
  • inner ear morphogenesis
  • negative regulation of osteoblast differentiation
  • positive regulation of MAP kinase activity
  • embryonic limb morphogenesis
  • sensory perception of sound
  • branching involved in salivary gland morphogenesis
  • regulation of lateral mesodermal cell fate specification
  • skeletal system development
  • fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development
  • small GTPase mediated signal transduction
  • phosphatidylinositol-mediated signaling
  • organ induction
Components
  • integral component of membrane
  • cytosol
  • integral component of plasma membrane
  • extracellular region
  • nucleus
  • cytoplasmic membrane-bounded vesicle
  • plasma membrane
  • receptor complex
General FunctionProtein tyrosine kinase activity
Specific FunctionTyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.
Pfam Domain Function
Transmembrane Regions377-397
GenBank Protein ID31368
UniProtKB IDP11362
UniProtKB Entry NameFGFR1_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0021960|Fibroblast growth factor receptor 1 (FGFR1)
ATGTGGAGCTGGAAGTGCCTCCTCTTCTGGGCTGTGCTGGTCACAGCCACACTCTGCACC
GCTAGGCCGTCCCCGACCTTGCCTGAACAAGCCCAGCCCTGGGGAGCCCCTGTGGAAGTG
GAGTCCTTCCTGGTCCACCCCGGTGACCTGCTGCAGCTTCGCTGTCGGCTGCGGGACGAT
GTGCAGAGCATCAACTGGCTGCGGGACGGGGTGCAGCTGGCGGAAAGCAACCGCACCCGC
ATCACAGGGGAGGAGGTGGAGGTGCAGGACTCCGTGCCCGCAGACTCCGGCCTCTATGCT
TGCGTAACCAGCAGCCCCTCGGGCAGTGACACCACCTACTTCTCCGTCAATGTTTCAGAT
GCTCTCCCCTCCTCGGAGGATGATGATGATGATGATGACTCCTCTTCAGAGGAGAAAGAA
ACAGATAACACCAAACCAAACCGTATGCCCGTAGCTCCATATTGGACATCCCCAGAAAAG
ATGGAAAAGAAATTGCATGCAGTGCCGGCTGCCAAGACAGTGAAGTTCAAATGCCCTTCC
AGTGGGACCCCAAACCCCACACTGCGCTGGTTGAAAAATGGCAAAGAATTCAAACCTGAC
CACAGAATTGGAGGCTACAAGGTCCGTTATGCCACCTGGAGCATCATAATGGACTCTGTG
GTGCCCTCTGACAAGGGCAACTACACCTGCATTGTGGAGAATGAGTACGGCAGCATCAAC
CACACATACCAGCTGGATGTCGTGGAGCGGTCCCCTCACCGGCCCATCCTGCAAGCAGGG
TTGCCCGCCAACAAAACAGTGGCCCTGGGTAGCAACGTGGAGTTCATGTGTAAGGTGTAC
AGTGACCCGCAGCCGCACATCCAGTGGCTAAAGCACATCGAGGTGAATGGGAGCAAGATT
GGCCCAGACAACCTGCCTTATGTCCAGATCTTGAAGACTGCTGGAGTTAATACCACCGAC
AAAGAGATGGAGGTGCTTCACTTAAGAAATGTCTCCTTTGAGGACGCAGGGGAGTATACG
TGCTTGGCGGGTAACTCTATCGGACTCTCCCATCACTCTGCATGGTTGACCGTTCTGGAA
GCCCTGGAAGAGAGGCCGGCAGTGATGACCTCGCCCCTGTACCTGGAGATCATCATCTAT
TGCACAGGGGCCTTCCTCATCTCCTGCATGGTGGGGTCGGTCATCGTCTACAAGATGAAG
AGTGGTACCAAGAAGAGTGACTTCCACAGCCAGATGGCTGTGCACAAGCTGGCCAAGAGC
ATCCCTCTGCGCAGACAGGTGTCTGCTGACTCCAGTGCATCCATGAACTCTGGGGTTCTT
CTGGTTCGGCCATCACGGCTCTCCTCCAGTGGGACTCCCATGCTAGCAGGGGTCTCTGAG
TATGAGCTTCCCGAAGACCCTCGCTGGGAGCTGCCTCGGGACAGACTGGTCTTAGGCAAA
CCCCTGGGAGAGGGCTGCTTTGGGCAGGTGGTGTTGGCAGAGGCTATCGGGCTGGACAAG
GACAAACCCAACCGTGTGACCAAAGTGGCTGTGAAGATGTTGAAGTCGGACGCAACAGAG
AAAGACTTGTCAGACCTGATCTCAGAAATGGAGATGATGAAGATGATCGGGAAGCATAAG
AATATCATCAACCTGCTGGGGGCCTGCACGCAGGATGGTCCCTTGTATGTCATCGTGGAG
TATGCCTCCAAGGGCAACCTGCGGGAGTACCTGCAGGCCCGGAGGCCCCCAGGGCTGGAA
TACTGCTACAACCCCAGCCACAACCCAGAGGAGCAGCTCTCCTCCAAGGACCTGGTGTCC
TGCGCCTACCAGGTGGCCCGAGGCATGGAGTATCTGGCCTCCAAGAAGTGCATACACCGA
GACCTGGCAGCCAGGAATGTCCTGGTGACAGAGGACAATGTGATGAAGATAGCAGACTTT
GGCCTCGCACGGGACATTCACCACATCGACTACTATAAAAAGACAACCAACGGCCGACTG
CCTGTGAAGTGGATGGCACCCGAGGCATTATTTGACCGGATCTACACCCACCAGAGTGAT
GTGTGGTCTTTCGGGGTGCTCCTGTGGGAGATCTTCACTCTGGGCGGCTCCCCATACCCC
GGTGTGCCTGTGGAGGAACTTTTCAAGCTGCTGAAGGAGGGTCACCGCATGGACAAGCCC
AGTAACTGCACCAACGAGCTGTACATGATGATGCGGGACTGCTGGCATGCAGTGCCCTCA
CAGAGACCCACCTTCAAGCAGCTGGTGGAAGACCTGGACCGCATCGTGGCCTTGACCTCC
AACCAGGAGTACCTGGACCTGTCCATGCCCCTGGACCAGTACTCCCCCAGCTTTCCCGAC
ACCCGGAGCTCTACGTGCTCCTCAGGGGAGGATTCCGTCTTCTCTCATGAGCCGCTGCCC
GAGGAGCCCTGCCTGCCCCGACACCCAGCCCAGCTTGCCAATGGCGGACTCAAACGCCGC
TGA
GenBank Gene IDX51803
GeneCard IDNot Available
GenAtlas IDFGFR1
HGNC IDHGNC:3688
Chromosome Location8
Locus8p11.2-p11.1
References
  1. Itoh N, Terachi T, Ohta M, Seo MK: The complete amino acid sequence of the shorter form of human basic fibroblast growth factor receptor deduced from its cDNA. Biochem Biophys Res Commun. 1990 Jun 15;169(2):680-5. 2162671
  2. Dionne CA, Crumley G, Bellot F, Kaplow JM, Searfoss G, Ruta M, Burgess WH, Jaye M, Schlessinger J: Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors. EMBO J. 1990 Sep;9(9):2685-92. 1697263
  3. Johnson DE, Lee PL, Lu J, Williams LT: Diverse forms of a receptor for acidic and basic fibroblast growth factors. Mol Cell Biol. 1990 Sep;10(9):4728-36. 2167437
  4. Isacchi A, Bergonzoni L, Sarmientos P: Complete sequence of a human receptor for acidic and basic fibroblast growth factors. Nucleic Acids Res. 1990 Apr 11;18(7):1906. 2159626
  5. Wennstrom S, Sandstrom C, Claesson-Welsh L: cDNA cloning and expression of a human FGF receptor which binds acidic and basic FGF. Growth Factors. 1991;4(3):197-208. 1722683
  6. Kiefer MC, Baird A, Nguyen T, George-Nascimento C, Mason OB, Boley LJ, Valenzuela P, Barr PJ: Molecular cloning of a human basic fibroblast growth factor receptor cDNA and expression of a biologically active extracellular domain in a baculovirus system. Growth Factors. 1991;5(2):115-27. 1662973
  7. Eisemann A, Ahn JA, Graziani G, Tronick SR, Ron D: Alternative splicing generates at least five different isoforms of the human basic-FGF receptor. Oncogene. 1991 Jul;6(7):1195-202. 1650441
  8. Hou JZ, Kan MK, McKeehan K, McBride G, Adams P, McKeehan WL: Fibroblast growth factor receptors from liver vary in three structural domains. Science. 1991 Feb 8;251(4994):665-8. 1846977
  9. Hattori Y, Odagiri H, Katoh O, Sakamoto H, Morita T, Shimotohno K, Tobinai K, Sugimura T, Terada M: K-sam-related gene, N-sam, encodes fibroblast growth factor receptor and is expressed in T-lymphocytic tumors. Cancer Res. 1992 Jun 15;52(12):3367-71. 1317750
  10. Miura K, Miura S, Yoshiura K, Seminara S, Hamaguchi D, Niikawa N, Masuzaki H: A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1. Hum Reprod. 2010 Apr;25(4):1076-80. doi: 10.1093/humrep/deq006. Epub 2010 Feb 6. 20139426
  11. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  12. Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M, Kodira CD, Schueler MG, Shimizu A, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Allen NR, Anderson S, Asakawa T, Blechschmidt K, Bloom T, Borowsky ML, Butler J, Cook A, Corum B, DeArellano K, DeCaprio D, Dooley KT, Dorris L 3rd, Engels R, Glockner G, Hafez N, Hagopian DS, Hall JL, Ishikawa SK, Jaffe DB, Kamat A, Kudoh J, Lehmann R, Lokitsang T, Macdonald P, Major JE, Matthews CD, Mauceli E, Menzel U, Mihalev AH, Minoshima S, Murayama Y, Naylor JW, Nicol R, Nguyen C, O'Leary SB, O'Neill K, Parker SC, Polley A, Raymond CK, Reichwald K, Rodriguez J, Sasaki T, Schilhabel M, Siddiqui R, Smith CL, Sneddon TP, Talamas JA, Tenzin P, Topham K, Venkataraman V, Wen G, Yamazaki S, Young SK, Zeng Q, Zimmer AR, Rosenthal A, Birren BW, Platzer M, Shimizu N, Lander ES: DNA sequence and analysis of human chromosome 8. Nature. 2006 Jan 19;439(7074):331-5. 16421571
  13. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  14. Pantoliano MW, Horlick RA, Springer BA, Van Dyk DE, Tobery T, Wetmore DR, Lear JD, Nahapetian AT, Bradley JD, Sisk WP: Multivalent ligand-receptor binding interactions in the fibroblast growth factor system produce a cooperative growth factor and heparin mechanism for receptor dimerization. Biochemistry. 1994 Aug 30;33(34):10229-48. 7520751
  15. Rusnati M, Coltrini D, Caccia P, Dell'Era P, Zoppetti G, Oreste P, Valsasina B, Presta M: Distinct role of 2-O-, N-, and 6-O-sulfate groups of heparin in the formation of the ternary complex with basic fibroblast growth factor and soluble FGF receptor-1. Biochem Biophys Res Commun. 1994 Aug 30;203(1):450-8. 8074689
  16. Johnson DE, Lu J, Chen H, Werner S, Williams LT: The human fibroblast growth factor receptor genes: a common structural arrangement underlies the mechanisms for generating receptor forms that differ in their third immunoglobulin domain. Mol Cell Biol. 1991 Sep;11(9):4627-34. 1652059
  17. Gutkind JS, Link DC, Katamine S, Lacal P, Miki T, Ley TJ, Robbins KC: A novel c-fgr exon utilized in Epstein-Barr virus-infected B lymphocytes but not in normal monocytes. Mol Cell Biol. 1991 Mar;11(3):1500-7. 1847500
  18. Mohammadi M, Honegger AM, Rotin D, Fischer R, Bellot F, Li W, Dionne CA, Jaye M, Rubinstein M, Schlessinger J: A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast growth factor receptor (Flg) is a binding site for the SH2 domain of phospholipase C-gamma 1. Mol Cell Biol. 1991 Oct;11(10):5068-78. 1656221
  19. Peters KG, Marie J, Wilson E, Ives HE, Escobedo J, Del Rosario M, Mirda D, Williams LT: Point mutation of an FGF receptor abolishes phosphatidylinositol turnover and Ca2+ flux but not mitogenesis. Nature. 1992 Aug 20;358(6388):678-81. 1379697
  20. Mohammadi M, Dionne CA, Li W, Li N, Spivak T, Honegger AM, Jaye M, Schlessinger J: Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without affecting mitogenesis. Nature. 1992 Aug 20;358(6388):681-4. 1379698
  21. Sorokin A, Mohammadi M, Huang J, Schlessinger J: Internalization of fibroblast growth factor receptor is inhibited by a point mutation at tyrosine 766. J Biol Chem. 1994 Jun 24;269(25):17056-61. 7516330
  22. Mohammadi M, Dikic I, Sorokin A, Burgess WH, Jaye M, Schlessinger J: Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction. Mol Cell Biol. 1996 Mar;16(3):977-89. 8622701
  23. Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M: Receptor specificity of the fibroblast growth factor family. J Biol Chem. 1996 Jun 21;271(25):15292-7. 8663044
  24. Reiter A, Sohal J, Kulkarni S, Chase A, Macdonald DH, Aguiar RC, Goncalves C, Hernandez JM, Jennings BA, Goldman JM, Cross NC: Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome. Blood. 1998 Sep 1;92(5):1735-42. 9716603
  25. DiGabriele AD, Lax I, Chen DI, Svahn CM, Jaye M, Schlessinger J, Hendrickson WA: Structure of a heparin-linked biologically active dimer of fibroblast growth factor. Nature. 1998 Jun 25;393(6687):812-7. 9655399
  26. Popovici C, Zhang B, Gregoire MJ, Jonveaux P, Lafage-Pochitaloff M, Birnbaum D, Pebusque MJ: The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to fibroblast growth factor receptor 1. Blood. 1999 Feb 15;93(4):1381-9. 9949182
  27. Wang J, Dai H, Yousaf N, Moussaif M, Deng Y, Boufelliga A, Swamy OR, Leone ME, Riedel H: Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis. Mol Cell Biol. 1999 Sep;19(9):6217-28. 10454568
  28. Guasch G, Mack GJ, Popovici C, Dastugue N, Birnbaum D, Rattner JB, Pebusque MJ: FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33). Blood. 2000 Mar 1;95(5):1788-96. 10688839
  29. Ong SH, Hadari YR, Gotoh N, Guy GR, Schlessinger J, Lax I: Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6074-9. Epub 2001 May 15. 11353842
  30. Cross MJ, Lu L, Magnusson P, Nyqvist D, Holmqvist K, Welsh M, Claesson-Welsh L: The Shb adaptor protein binds to tyrosine 766 in the FGFR-1 and regulates the Ras/MEK/MAPK pathway via FRS2 phosphorylation in endothelial cells. Mol Biol Cell. 2002 Aug;13(8):2881-93. 12181353
  31. Grand EK, Grand FH, Chase AJ, Ross FM, Corcoran MM, Oscier DG, Cross NC: Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome. Genes Chromosomes Cancer. 2004 May;40(1):78-83. 15034873
  32. Hu Y, Fang X, Dunham SM, Prada C, Stachowiak EK, Stachowiak MK: 90-kDa ribosomal S6 kinase is a direct target for the nuclear fibroblast growth factor receptor 1 (FGFR1): role in FGFR1 signaling. J Biol Chem. 2004 Jul 9;279(28):29325-35. Epub 2004 Apr 26. 15117958
  33. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. 16335952
  34. Gu TL, Goss VL, Reeves C, Popova L, Nardone J, Macneill J, Walters DK, Wang Y, Rush J, Comb MJ, Druker BJ, Polakiewicz RD: Phosphotyrosine profiling identifies the KG-1 cell line as a model for the study of FGFR1 fusions in acute myeloid leukemia. Blood. 2006 Dec 15;108(13):4202-4. Epub 2006 Aug 31. 16946300
  35. Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM: Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem. 2006 Jun 9;281(23):15694-700. Epub 2006 Apr 4. 16597617
  36. Dunham-Ems SM, Pudavar HE, Myers JM, Maher PA, Prasad PN, Stachowiak MK: Factors controlling fibroblast growth factor receptor-1's cytoplasmic trafficking and its regulation as revealed by FRAP analysis. Mol Biol Cell. 2006 May;17(5):2223-35. Epub 2006 Feb 15. 16481405
  37. Furdui CM, Lew ED, Schlessinger J, Anderson KS: Autophosphorylation of FGFR1 kinase is mediated by a sequential and precisely ordered reaction. Mol Cell. 2006 Mar 3;21(5):711-7. 16507368
  38. Dong S, Kang S, Gu TL, Kardar S, Fu H, Lonial S, Khoury HJ, Khuri F, Chen J: 14-3-3 Integrates prosurvival signals mediated by the AKT and MAPK pathways in ZNF198-FGFR1-transformed hematopoietic cells. Blood. 2007 Jul 1;110(1):360-9. Epub 2007 Mar 27. 17389761
  39. Kurosu H, Choi M, Ogawa Y, Dickson AS, Goetz R, Eliseenkova AV, Mohammadi M, Rosenblatt KP, Kliewer SA, Kuro-o M: Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem. 2007 Sep 14;282(37):26687-95. Epub 2007 Jul 10. 17623664
  40. Citores L, Bai L, Sorensen V, Olsnes S: Fibroblast growth factor receptor-induced phosphorylation of STAT1 at the Golgi apparatus without translocation to the nucleus. J Cell Physiol. 2007 Jul;212(1):148-56. 17311277
  41. Haugsten EM, Malecki J, Bjorklund SM, Olsnes S, Wesche J: Ubiquitination of fibroblast growth factor receptor 1 is required for its intracellular sorting but not for its endocytosis. Mol Biol Cell. 2008 Aug;19(8):3390-403. doi: 10.1091/mbc.E07-12-1219. Epub 2008 May 14. 18480409
  42. Hu Y, Guimond SE, Travers P, Cadman S, Hohenester E, Turnbull JE, Kim SH, Bouloux PM: Novel mechanisms of fibroblast growth factor receptor 1 regulation by extracellular matrix protein anosmin-1. J Biol Chem. 2009 Oct 23;284(43):29905-20. doi: 10.1074/jbc.M109.049155. Epub 2009 Aug 20. 19696444
  43. Dunham-Ems SM, Lee YW, Stachowiak EK, Pudavar H, Claus P, Prasad PN, Stachowiak MK: Fibroblast growth factor receptor-1 (FGFR1) nuclear dynamics reveal a novel mechanism in transcription control. Mol Biol Cell. 2009 May;20(9):2401-12. doi: 10.1091/mbc.E08-06-0600. Epub 2009 Mar 4. 19261810
  44. Lew ED, Furdui CM, Anderson KS, Schlessinger J: The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations. Sci Signal. 2009 Feb 17;2(58):ra6. doi: 10.1126/scisignal.2000021. 19224897
  45. Goetz R, Nakada Y, Hu MC, Kurosu H, Wang L, Nakatani T, Shi M, Eliseenkova AV, Razzaque MS, Moe OW, Kuro-o M, Mohammadi M: Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation. Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):407-12. doi: 10.1073/pnas.0902006107. Epub 2009 Dec 4. 19966287
  46. Persaud A, Alberts P, Hayes M, Guettler S, Clarke I, Sicheri F, Dirks P, Ciruna B, Rotin D: Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function. EMBO J. 2011 Jul 15;30(16):3259-73. doi: 10.1038/emboj.2011.234. 21765395
  47. Groth C, Lardelli M: The structure and function of vertebrate fibroblast growth factor receptor 1. Int J Dev Biol. 2002;46(4):393-400. 12141425
  48. Eswarakumar VP, Lax I, Schlessinger J: Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005 Apr;16(2):139-49. Epub 2005 Feb 1. 15863030
  49. Turner N, Grose R: Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010 Feb;10(2):116-29. doi: 10.1038/nrc2780. 20094046
  50. Hu Y, Bouloux PM: Novel insights in FGFR1 regulation: lessons from Kallmann syndrome. Trends Endocrinol Metab. 2010 Jun;21(6):385-93. doi: 10.1016/j.tem.2010.01.004. Epub 2010 Feb 1. 20117945
  51. Mohammadi M, Schlessinger J, Hubbard SR: Structure of the FGF receptor tyrosine kinase domain reveals a novel autoinhibitory mechanism. Cell. 1996 Aug 23;86(4):577-87. 8752212
  52. Mohammadi M, McMahon G, Sun L, Tang C, Hirth P, Yeh BK, Hubbard SR, Schlessinger J: Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science. 1997 May 9;276(5314):955-60. 9139660
  53. Plotnikov AN, Hubbard SR, Schlessinger J, Mohammadi M: Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity. Cell. 2000 May 12;101(4):413-24. 10830168
  54. Schlessinger J, Plotnikov AN, Ibrahimi OA, Eliseenkova AV, Yeh BK, Yayon A, Linhardt RJ, Mohammadi M: Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Mol Cell. 2000 Sep;6(3):743-50. 11030354
  55. Bae JH, Lew ED, Yuzawa S, Tome F, Lax I, Schlessinger J: The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site. Cell. 2009 Aug 7;138(3):514-24. doi: 10.1016/j.cell.2009.05.028. 19665973
  56. Bae JH, Boggon TJ, Tome F, Mandiyan V, Lax I, Schlessinger J: Asymmetric receptor contact is required for tyrosine autophosphorylation of fibroblast growth factor receptor in living cells. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2866-71. doi: 10.1073/pnas.0914157107. Epub 2010 Jan 26. 20133753
  57. Eathiraj S, Palma R, Hirschi M, Volckova E, Nakuci E, Castro J, Chen CR, Chan TC, France DS, Ashwell MA: A novel mode of protein kinase inhibition exploiting hydrophobic motifs of autoinhibited kinases: discovery of ATP-independent inhibitors of fibroblast growth factor receptor. J Biol Chem. 2011 Jun 10;286(23):20677-87. doi: 10.1074/jbc.M110.213736. Epub 2011 Mar 24. 21454610
  58. Muenke M, Schell U, Hehr A, Robin NH, Losken HW, Schinzel A, Pulleyn LJ, Rutland P, Reardon W, Malcolm S, et al.: A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome. Nat Genet. 1994 Nov;8(3):269-74. 7874169
  59. Kress W, Petersen B, Collmann H, Grimm T: An unusual FGFR1 mutation (fibroblast growth factor receptor 1 mutation) in a girl with non-syndromic trigonocephaly. Cytogenet Cell Genet. 2000;91(1-4):138-40. 11173846
  60. Dode C, Levilliers J, Dupont JM, De Paepe A, Le Du N, Soussi-Yanicostas N, Coimbra RS, Delmaghani S, Compain-Nouaille S, Baverel F, Pecheux C, Le Tessier D, Cruaud C, Delpech M, Speleman F, Vermeulen S, Amalfitano A, Bachelot Y, Bouchard P, Cabrol S, Carel JC, Delemarre-van de Waal H, Goulet-Salmon B, Kottler ML, Richard O, Sanchez-Franco F, Saura R, Young J, Petit C, Hardelin JP: Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet. 2003 Apr;33(4):463-5. Epub 2003 Mar 10. 12627230
  61. Sato N, Katsumata N, Kagami M, Hasegawa T, Hori N, Kawakita S, Minowada S, Shimotsuka A, Shishiba Y, Yokozawa M, Yasuda T, Nagasaki K, Hasegawa D, Hasegawa Y, Tachibana K, Naiki Y, Horikawa R, Tanaka T, Ogata T: Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients. J Clin Endocrinol Metab. 2004 Mar;89(3):1079-88. 15001591
  62. White KE, Cabral JM, Davis SI, Fishburn T, Evans WE, Ichikawa S, Fields J, Yu X, Shaw NJ, McLellan NJ, McKeown C, Fitzpatrick D, Yu K, Ornitz DM, Econs MJ: Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation. Am J Hum Genet. 2005 Feb;76(2):361-7. Epub 2004 Dec 28. 15625620
  63. Albuisson J, Pecheux C, Carel JC, Lacombe D, Leheup B, Lapuzina P, Bouchard P, Legius E, Matthijs G, Wasniewska M, Delpech M, Young J, Hardelin JP, Dode C: Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2). Hum Mutat. 2005 Jan;25(1):98-9. 15605412
  64. Sato N, Hasegawa T, Hori N, Fukami M, Yoshimura Y, Ogata T: Gonadotrophin therapy in Kallmann syndrome caused by heterozygous mutations of the gene for fibroblast growth factor receptor 1: report of three families: case report. Hum Reprod. 2005 Aug;20(8):2173-8. Epub 2005 Apr 21. 15845591
  65. Farrow EG, Davis SI, Mooney SD, Beighton P, Mascarenhas L, Gutierrez YR, Pitukcheewanont P, White KE: Extended mutational analyses of FGFR1 in osteoglophonic dysplasia. Am J Med Genet A. 2006 Mar 1;140(5):537-9. 16470795
  66. Trarbach EB, Costa EM, Versiani B, de Castro M, Baptista MT, Garmes HM, de Mendonca BB, Latronico AC: Novel fibroblast growth factor receptor 1 mutations in patients with congenital hypogonadotropic hypogonadism with and without anosmia. J Clin Endocrinol Metab. 2006 Oct;91(10):4006-12. Epub 2006 Aug 1. 16882753
  67. Pitteloud N, Meysing A, Quinton R, Acierno JS Jr, Dwyer AA, Plummer L, Fliers E, Boepple P, Hayes F, Seminara S, Hughes VA, Ma J, Bouloux P, Mohammadi M, Crowley WF Jr: Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes. Mol Cell Endocrinol. 2006 Jul 25;254-255:60-9. Epub 2006 Jun 9. 16764984
  68. Zenaty D, Bretones P, Lambe C, Guemas I, David M, Leger J, de Roux N: Paediatric phenotype of Kallmann syndrome due to mutations of fibroblast growth factor receptor 1 (FGFR1). Mol Cell Endocrinol. 2006 Jul 25;254-255:78-83. Epub 2006 Jun 6. 16757108
  69. Pitteloud N, Acierno JS Jr, Meysing A, Eliseenkova AV, Ma J, Ibrahimi OA, Metzger DL, Hayes FJ, Dwyer AA, Hughes VA, Yialamas M, Hall JE, Grant E, Mohammadi M, Crowley WF Jr: Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6281-6. Epub 2006 Apr 10. 16606836
  70. Dode C, Fouveaut C, Mortier G, Janssens S, Bertherat J, Mahoudeau J, Kottler ML, Chabrolle C, Gancel A, Francois I, Devriendt K, Wolczynski S, Pugeat M, Pineiro-Garcia A, Murat A, Bouchard P, Young J, Delpech M, Hardelin JP: Novel FGFR1 sequence variants in Kallmann syndrome, and genetic evidence that the FGFR1c isoform is required in olfactory bulb and palate morphogenesis. Hum Mutat. 2007 Jan;28(1):97-8. 17154279
  71. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. 17344846
  72. Raivio T, Sidis Y, Plummer L, Chen H, Ma J, Mukherjee A, Jacobson-Dickman E, Quinton R, Van Vliet G, Lavoie H, Hughes VA, Dwyer A, Hayes FJ, Xu S, Sparks S, Kaiser UB, Mohammadi M, Pitteloud N: Impaired fibroblast growth factor receptor 1 signaling as a cause of normosmic idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2009 Nov;94(11):4380-90. doi: 10.1210/jc.2009-0179. Epub 2009 Oct 9. 19820032
  73. Tornberg J, Sykiotis GP, Keefe K, Plummer L, Hoang X, Hall JE, Quinton R, Seminara SB, Hughes V, Van Vliet G, Van Uum S, Crowley WF, Habuchi H, Kimata K, Pitteloud N, Bulow HE: Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11524-9. doi: 10.1073/pnas.1102284108. Epub 2011 Jun 23. 21700882
  74. Hanchate NK, Giacobini P, Lhuillier P, Parkash J, Espy C, Fouveaut C, Leroy C, Baron S, Campagne C, Vanacker C, Collier F, Cruaud C, Meyer V, Garcia-Pinero A, Dewailly D, Cortet-Rudelli C, Gersak K, Metz C, Chabrier G, Pugeat M, Young J, Hardelin JP, Prevot V, Dode C: SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome. PLoS Genet. 2012 Aug;8(8):e1002896. doi: 10.1371/journal.pgen.1002896. Epub 2012 Aug 23. 22927827
  75. Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, Beenken A, Clarke J, Pers TH, Dworzynski P, Keefe K, Niedziela M, Raivio T, Crowley WF Jr, Seminara SB, Quinton R, Hughes VA, Kumanov P, Young J, Yialamas MA, Hall JE, Van Vliet G, Chanoine JP, Rubenstein J, Mohammadi M, Tsai PS, Sidis Y, Lage K, Pitteloud N: Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013 May 2;92(5):725-43. doi: 10.1016/j.ajhg.2013.04.008. 23643382
  76. Simonis N, Migeotte I, Lambert N, Perazzolo C, de Silva DC, Dimitrov B, Heinrichs C, Janssens S, Kerr B, Mortier G, Van Vliet G, Lepage P, Casimir G, Abramowicz M, Smits G, Vilain C: FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly. J Med Genet. 2013 Sep;50(9):585-92. doi: 10.1136/jmedgenet-2013-101603. Epub 2013 Jun 28. 23812909
  77. Dhamija R, Kirmani S, Wang X, Ferber MJ, Wieben ED, Lazaridis KN, Babovic-Vuksanovic D: Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield syndrome: a case of gonadal mosaicism. Am J Med Genet A. 2014 Sep;164A(9):2356-9. doi: 10.1002/ajmg.a.36621. Epub 2014 May 28. 24888332
  78. Marcos S, Sarfati J, Leroy C, Fouveaut C, Parent P, Metz C, Wolczynski S, Gerard M, Bieth E, Kurtz F, Verier-Mine O, Perrin L, Archambeaud F, Cabrol S, Rodien P, Hove H, Prescott T, Lacombe D, Christin-Maitre S, Touraine P, Hieronimus S, Dewailly D, Young J, Pugeat M, Hardelin JP, Dode C: The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients. J Clin Endocrinol Metab. 2014 Oct;99(10):E2138-43. doi: 10.1210/jc.2014-2110. Epub 2014 Jul 31. 25077900
  79. Goncalves C, Bastos M, Pignatelli D, Borges T, Aragues JM, Fonseca F, Pereira BD, Socorro S, Lemos MC: Novel FGFR1 mutations in Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism: evidence for the involvement of an alternatively spliced isoform. Fertil Steril. 2015 Nov;104(5):1261-7.e1. doi: 10.1016/j.fertnstert.2015.07.1142. Epub 2015 Aug 12. 26277103