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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.