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FGF Site: FGF Intro Nomenclature Notes FGF Sequences FGFR Sequences
The kinemages on this site were based on these FGF Structure References:
P. Bellosta, A. Iwahori,, A.N. Plotnikov, A.V. Eliseenkova, C. Basilico, M. Mohammadi, M. (2001, Identification of receptor and heparin binding sites in fibroblast growth factor 4 by structure-based mutagenesis. Mol.Cell Biol. 21, 5946-5957.
M. Blaner, J. Disalvo, K.A. Thomas, (1996), X-Ray Crystal Structure of Human Acidic Fibroblast Growth Factor, Biochemistry, 35, 2086-2084.
A.D. Digabriele, I. Lax, D.I. Chen, C.M. Svahn, M. Jaye, J. Schlessinger, W.A.
Hendrickson, (1998), Structure of a heparin-linked biologically active dimer of fibroblast growth factor, Nature, (393), 812- 817.
S. Faham, R.E. Hileman, J.R. Fromm, R.J. Linhardt, D.C.
Rees, (1996), Heparin Structure and Interactions with Basic Fibroblast Growth Factor. Science, 271,1116-1120.
N.J. Harmer, L. Pellegrini, D. Chirgadze, J .Fernandez-Recio, T.L. Blundell, (2004), The Crystal Structure of Fibroblast Growth Factor (FGF) 19 Reveals Novel Features of the FGF Family and Offers for its Unusual Receptor Affinity, Biochemistry, 48, 629-640.
H.J. Hecht, R. Adar, H. Hofmann, O. Bogin, H. Weich, A. Yayon, (2001), Structure of fibroblast growth factor 9 shows a symmetric dimer with unique receptor-and heparin-binding interfaces, Acta Crystallogr. D57, 378-384.
H.M. Holden, M. Ito, D.J. Hartshorne, I. Rayment, (1999), X-Ray Structure determination of Telokin, the C-Terminal Domain of Myosin Light Chain Kinase at 2.8 Angstroms Resolution, J.Mol.Biol. 227, 840-851.
J.S. Kastrup, E.S. Eriksson, H. Dalbogen, H. Flodgaard, (1997), X-ray structure of the 154-amino-acid form of recombinant human basic fibroblast growth factor: Comparison with the truncated 146-amino-acid form. Acta Crystallogr D Biol Crystallogr 53, 160-168.
R.M. Lozano, M. Jimenez, J. Santoro, M. Rico, G. Gimenez-gallego, (1998), Solution structure of acidic fibroblast growth factor bound to 1,3,6-naphthalene trisulphonate: a minimal model for the anti-tumoral action of suramins and suradistas, J. Mol. Biol. 281, 899-015.
R.M. Lozano, A. Pineda-Lucena, C. Gonzalez, M.A. Jimenez, P.Cuevas, M. Redonde-Horcajo, J.M. Sanz, M. Rico, G. Gimenez-Gallego, (2000), 1H-NMR Structural Characterization of a Nonmitogenic, Vasodilatory, Ischemia-Protector and Neuromodulatory Acidic Fibroblast Growth Factor, Biochemistry, 39, 4982-4993
Y. Luo, W. Lu, K.A. Mohamedali, J.H. Jang, R.B. Jones, J.L. Gabriel, M. Kan, W.L. Mckeehan, (1998), The glycine box: a determinant of specificity for fibroblast growth factor, Biochemistry, (37), 16506-16515.
M. Mohammadi, S. Froum, J.M. Hamby, M. Schroeder, R.L. Panek, G.H. Lu, A.V. Eliseenkova, D. Green, J. Schlessinger, S.R. Hubbard, (1998), Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain, EMBO J. 17(20), 5896-5904.
M. Mohammadi , S. K. Olsen, O. A. Ibrahimi, (2005), Structural basis for fibroblast growth factor receptor activation, Cytokine & Growth Factor Reviews 16, 107–137.
M. Mohammadi, G. McMahon, L. Sun, C. Tang, P. Hirth, B.K. Yeh, S. Hubbard, J. Schlessinger, (1997), Structures of the Tyrosine Kinase Domain of Fibroblast Growth Factor Receptor in Complex with Inhibitors, Science, (276), 955-960.
M. Mohammadi, J. Schlessinger. S. Hubbard. (1996), Structure of the FGF Receptor Tyrosine Kinase Domain Reveals a Novel Autioinhibitory Mechanism, Cell, 86, 677-687.
S.K. Olsen, M. Garbi, N. Zampieri, A. Eliseenkova, D.M. Orniitz, M. Goldfarb, M. Mohammadi, (2003), Fibroblast Growth Factor (FGF) Homologous Factors Share Structural, but Not Functional Homology with FGFs, J Biol Chem. 278(36), 34226-34236.
S.K. Olsen, O.A. Ibrahimi, A. Raucci, F. Zhang, A.V. Eliseenkova, A. Yayon, C. Basilico, R.J. Linhardt, J. Schlessinger, M. Mohammadi, (2004),Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity, Proc.Nat.Acad.Sci.USA, 101, 935-940.
S.K. Olsen, J.Y.H. Li, C. Bromleigh, A.V. Eliseenkova, O. A. Ibrahimi, Z. Lao, F. Zhang, R. J. Linhardt, A. L. Joyner and M. Mohammadi, (2006), Structural basis by which alternative splicing modulates the organizer activity of FGF 8 in the brain, Genes & Dev. 20, 185-198.
D.M. Ornitz, N. Itoh (2001), Fibroblast growth factors, Genome Biology, 2(3), Reviews, 3005, 1-3005.12.
A.N. Plotnikov, A.V. Eliseenkova, O.A. Ibrahimi, M.A. Lemmon, M. Mohammadi. (2001), Crystal Structure of Fibroblast Growth Factor 9 Reveals Regions Implicated in Dimerization and Autoinhibition, J.Biol.Chem. 276, 4322-4329.
A.N. Plotnikov, S.R. Hubbard, J. Schlessinger, M. Mohammadi, (2000), Crystal Structures of two FGF-FGFR Complexes Reveal the Determinants of Ligand-Receptor Specificity, Cell, 101, 413-424.
A.N. Plotnikov, J. Schlessinger, S.R. Hubbard, M. Mohammadi, (1999), Structural Basis of FGF Receptor Dimerization and Activation, Cell (Cambridge, MA), 98, 641-650.
R. Raman, G. Venkataraman, S. Ernst , V. Sasisekharan , R. Sasisekharan, (2003), Structural specificity of heparin binding in the fibroblast growth factor family of proteins, PNAS 100 (5), 2357–2362.
J. Schlessinger, A.N. Plotnikov, O.A. Ibrahimi, A.V. Eliseenkova, B.K.Yeh,
A.Yayon, C.J.Linhardt, M. Mohammadi, (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), 743-750.
D.J. Stauber, A.D. Digabriele, W.A. Hendrickson, (2000) Structural Interactions of Fibroblast Growth Factor Receptor with its Ligands, Proc.Nat.Acad.Sci. USA, 97, 49-54.
S. Ye, V. Luo, W. Lu, R.B. Jones, R.J. Linhardt, I.
Capila, T. Toida, M. Kan, H. Pelletier,
W.L. Mckeehan, (2001),
Basis for interaction of FGF-1, FGF-2, and FGF-7 with different heparan sulfate motifs, Biochemistry, (40), 14429-14439.
B.K. Yeh, M. Igarashi, A.V. Eliseenkova, A.N. Plotnikov, I. Sher, D. Ron, S.A. Aronson, M. Mohammadi, (2003), Structural Basis by which Alternative Splicing Confers Specificity in Fibroblast Growth Factor Receptors, Proc.Nat.Acad.Sci.USA, 100 (March 4). 2266-2271.
P. Aloy, R. B. Russell, (2006), Structural systems biology: modeling protein interactions, Nature Reviews Molecular Cell Biology, 7, 188-197,
A. Baird, P. Bohlen (1990) "Fibroblast Growth Factors" in Peptide Growth Factors and their Receptors, M.C. Sporn, A.B. Roberts, (ed.), Springer-Verlag, New York, 369-418.
R. A. Bradshaw, R. Fujii, H. Hondermarck, S. Raffioni, Y. Wu, M. A. Yarski, (1994), Polypeptide growth factors: Structure, function and mechanism of action, Pure & Appl. Chem., 66(1), 9-14.
S. Braun, U. Keller, H. Steiling, S. Werner, (2004), Fibroblast growth factors in epithelial repair and cytoprotection, Phil. Trans. R. Soc. Lond. B, 359, 753–757.
L. Chen, C-X, Deng, (2005), Roles Of FGF Signaling in Skeletal Development and Human Genetic Diseases, Frontiers in Bioscience 10, 1961-1976.
D.E. Johnson, L,T. Williams, (1993), Structural and functional diversity in the FGF receptor multigene family, Adv. Cancer Res,, 60, 1-41.
C. Basilicom D. Moscatelli, (1992), The FGF family of growth factors and oncogenes, Adv.Cancer Res.,59, 115-65.
M. Goldfarb, (2005), Fibroblast growth factor homologous factors: evolution, structure, and function, .Cytokine Growth Factor Rev. 16(2), 215-220
C. Groth, M. Lardelli, (2002), The structure and function of vertebrate Fibroblast Growth Factor Receptor 1, Int. J. Dev. Biol. 46: 393-400.
K. L. Kramer, H. J. Yost, (2003), Heparin Sulfate Core Proteins in Cell-Cell Signaling, Annu. Rev. Genet., 37, 461–84.
E. M. Munoz, R. J. Linhardt, (2004). Heparin-Binding Domains in Vascular Biology, Arterioscler Thromb Vasc Biol. 24, 1549-1557.
C J Powers, S W McLeskey and A Wellstein. (2000), Fibroblast growth factors, their receptors and signaling, Endocrine-Related Cancer, 7, 165–197.
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M.A. Riva, R. .Molteni, F. Bedogni, G. Racagni, F. Fumagalli, (2005), Emerging role of the FGF system in psychiatric disorders, Trends, Pharmacol. Sci. 26(5), 228-231.
C. A. Turner, H. Akil, S. J. Watson, S. J. Evans (2006), The Fibroblast Growth Factor System and Mood Disorders, Biol. Psychiatry, 59(12), 1128-1135.
Y. Yamashita (2005), Structural and Biochemical Properties of Fibroblast Growth Factor 23, Ther. Apher. Dial., 313-318.
G. Venkataraman, R. Raman, V. Sasisekharan, R. Sasisekharan, (1999), Molecular characteristics of fibroblast growth factor–fibroblast growth factor receptor–heparin-like glycosaminoglycan complex, Proc. Natl. Acad. Sci. USA, 96, 3658–3663.
NCAM References
V.V. Kiselyov, G. Skladchikova, A.M. Hinsby, P.H. Jensen, N. Kulahin, V. Soroka, N. Pedersen, V. Tsetlin, F.M. Poulsen, V. Berezin, E. Bock. (2003), Structural basis for a direct interaction between FGFR1 and NCAM and evidence for a regulatory role of ATP, Structure, 11, 691-701.
V. Soroka, K. Kolkova, J.S. Kastrup, K. Diederichs, J. Breed, V.V. Kiselyov, F.M.
Poulsen, I.K. Larsen, W. Welte, V. Berezin, E. Bock, C. Kasper. (2003), Structure and interactions of NCAM Ig1-2-3 suggest a novel zipper mechanism for homophilic adhesion, Structure, 11, 1291-1301.
Software Used
Creating Kinemages: PreKin and the text editor NoteTab
Evolutionary Tree: Output from Clustal X rendered in Tree View (Windows)
Helical Wheel Plot: Peptide Companion (Windows)
Molecular Modeling: Deep View (Windows), AccelyrSys Viewer Lite (Windows), .and SYBYL (Linux)
Sequence Alignments: Clustal X (Windows)
Screen Capture: Hypersnap DX (Windows) and Captura (Linux)
HTML Editor: Front Page
Web-Site Rendering of Kinemages: KiNG
"Artistic" renderings of FGF molecules Kaleidoscope feature of MAGE
Shockwave Animation: CamStudio
FGF Site: FGF Intro Nomenclature Notes FGF Sequences FGFR Sequences
My University Home Harris Links Chemistry / Modeling Links
Supported by the Pritzker Neuropsychiatric Disorders Research Consortium, and by NIH Grant 5 P01 MH42251, Conte Center Grant #L99MH60398, RO1 DA13386 and the Office of Naval Research (ONR) N00014-02-1-0879 to Huda Akil & Stanley J. Watson. at the Molecular & Behavioral Neuroscience Institute.