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Science 21 April 1995:
Vol. 268. no. 5209, pp. 432 - 436
DOI: 10.1126/science.7536345
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Articles

Science, Vol 268, Issue 5209, 432-436
Copyright © 1995 by American Association for the Advancement of Science

articles

FGF binding and FGF receptor activation by synthetic heparan-derived di- and trisaccharides

DM Ornitz, AB Herr, M Nilsson, J Westman, CM Svahn, and G Waksman

Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, MO 63110, USA.

Fibroblast growth factors (FGFs) require a polysaccharide cofactor, heparin or heparan sulfate (HS), for receptor binding and activation. To probe the molecular mechanism by which heparin or HS (heparin/HS) activates FGF, small nonsulfated oligosaccharides found within heparin/HS were assayed for activity. These synthetic and isomerically pure compounds can activate the FGF signaling pathway. The crystal structures of complexes between FGF and these heparin/HS oligosaccharides reveal several binding sites on FGF and constrain possible mechanisms by which heparin/HS can activate the FGF receptor. These studies establish a framework for the molecular design of compounds capable of modulating FGF activity.


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Divalent Cations and Heparin/Heparan Sulfate Cooperate to Control Assembly and Activity of the Fibroblast Growth Factor Receptor Complex.
M. Kan, F. Wang, M. Kan, B. To, J. L. Gabriel, and W. L. McKeehan (1996)
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Receptor Specificity of the Fibroblast Growth Factor Family.
D. M. Ornitz, J. Xu, J. S. Colvin, D. G. McEwen, C. A. MacArthur, F. Coulier, G. Gao, and M. Goldfarb (1996)
J. Biol. Chem. 271, 15292-15297
   Abstract »    Full Text »    PDF »
Sulfate Moieties in the Subendothelial Extracellular Matrix Are Involved in Basic Fibroblast Growth Factor Sequestration, Dimerization, and Stimulation of Cell Proliferation.
H.-Q. Miao, R. Ishai-Michaeli, R. Atzmon, T. Peretz, and I. Vlodavsky (1996)
J. Biol. Chem. 271, 4879-4886
   Abstract »    Full Text »    PDF »
Expression and Biological Activity of Mouse Fibroblast Growth Factor-9.
S. Santos-Ocampo, J. S. Colvin, A. Chellaiah, and D. M. Ornitz (1996)
J. Biol. Chem. 271, 1726-1731
   Abstract »    Full Text »    PDF »
Initial characterization of anosmin-1, a putative extracellular matrix protein synthesized by definite neuronal cell populations in the central nervous system.
N Soussi-Yanicostas, J. Hardelin, M. Arroyo-Jimenez, O Ardouin, R Legouis, J Levilliers, F Traincard, J. Betton, L Cabanie, and C Petit (1996)
J. Cell Sci. 109, 1749-1757
   Abstract »    PDF »
Heparan Sulfates Mediate the Binding of Basic Fibroblast Growth Factor to a Specific Receptor on Neural Precursor Cells.
Y. G. Brickman, M. D. Ford, D. H. Small, P. F. Bartlett, and V. Nurcombe (1995)
J. Biol. Chem. 270, 24941-24948
   Abstract »    Full Text »    PDF »
Receptor Binding and Mitogenic Properties of Mouse Fibroblast Growth Factor 3.
M. Mathieu, E. Chatelain, D. Ornitz, J. Bresnick, I. Mason, P. Kiefer, and C. Dickson (1995)
J. Biol. Chem. 270, 24197-24203
   Abstract »    Full Text »    PDF »
Glu-96 of Basic Fibroblast Growth Factor Is Essential for High Affinity Receptor Binding.
H. Zhu, K. Ramnarayan, J. Anchin, W. Y. Miao, A. Sereno, L. Millman, J. Zheng, V. N. Balaji, and M. E. Wolff (1995)
J. Biol. Chem. 270, 21869-21874
   Abstract »    Full Text »    PDF »
The Proliferative and Migratory Activities of Breast Cancer Cells Can Be Differentially Regulated by Heparan Sulfates.
V. Nurcombe, C. E. Smart, H. Chipperfield, S. M. Cool, B. Boilly, and H. Hondermarck (2000)
J. Biol. Chem. 275, 30009-30018
   Abstract »    Full Text »    PDF »
Preparation of Completely 6-O-Desulfated Heparin and Its Ability to Enhance Activity of Basic Fibroblast Growth Factor.
Y. Kariya, M. Kyogashima, K. Suzuki, T. Isomura, T. Sakamoto, K. Horie, M. Ishihara, R. Takano, K. Kamei, and S. Hara (2000)
J. Biol. Chem. 275, 25949-25958
   Abstract »    Full Text »    PDF »
Probing Fibroblast Growth Factor Dimerization and Role of Heparin-like Glycosaminoglycans in Modulating Dimerization and Signaling.
C.-P. Kwan, G. Venkataraman, Z. Shriver, R. Raman, D. Liu, Y. Qi, L. Varticovski, and R. Sasisekharan (2001)
J. Biol. Chem. 276, 23421-23429
   Abstract »    Full Text »    PDF »
Dissociation of Heparan Sulfate and Receptor Binding Domains of Hepatocyte Growth Factor Reveals That Heparan Sulfate-c-Met Interaction Facilitates Signaling.
J. S. Rubin, R. M. Day, D. Breckenridge, N. Atabey, W. G. Taylor, S. J. Stahl, P. T. Wingfield, J. D. Kaufman, R. Schwall, and D. P. Bottaro (2001)
J. Biol. Chem. 276, 32977-32983
   Abstract »    Full Text »    PDF »
Differential Effects of Heparin Saccharides on the Formation of Specific Fibroblast Growth Factor (FGF) and FGF Receptor Complexes.
O. Ostrovsky, B. Berman, J. Gallagher, B. Mulloy, D. G. Fernig, M. Delehedde, and D. Ron (2002)
J. Biol. Chem. 277, 2444-2453
   Abstract »    Full Text »    PDF »


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