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Activating and inhibitory heparin sequences for FGF-2 (basic FGF). Distinct requirements for FGF-1, FGF-2, and FGF-4.

Guimond, S, Maccarana, M, Olwin, B.B., Lindahl, U, Rapraeger, A.C.·1993·Journal of Biological Chemistry
DOI 10.1016/s0021-9258(20)80471-2
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Abstract

Chlorate-treated Swiss 3T3 fibroblasts, with impaired synthesis of heparan sulfate proteoglycan, were used as target cells in assessing the ability of exogenous heparin-derived saccharides to promote the mitogenic activity of basic fibroblast growth factor 2 (FGF-2). Full-size native heparin (carrying iduronosyl 2-O-sulfate and glucosaminyl 6-O-sulfate groups), as well as a dodecasaccharide fraction isolated after limited deaminative cleavage of heparin, were efficient promoters, whereas the corresponding decasaccharides, or smaller oligosaccharides, were inactive. Neither selectively 2-O-desulfated nor preferentially 6-O-desulfated heparin were active. However, the latter derivative competed with native heparin for binding to FGF-2 and thus blocked the ability of native heparin to promote the mitogenic activity of FGF-2. The 6-O-desulfated heparin also prevented the ability of FGF-2 to suppress myogenic differentiation in MM14 mouse myoblasts. The binding region for FGF-2 has been identified as a pentasaccharide sequence containing a single essential O-sulfate group, at C2 of iduronic acid (1). It is proposed that the dodecasaccharide sequence required to promote receptor signaling by FGF-2 encompasses this pentasaccharide region, which binds the growth factor, and a site interacting with the receptor that contains essential 2-O- and 6-O-sulfate groups. Similar studies involving the related growth factors, FGF-1 and FGF-4, revealed differential effects of saccharides. The mi…

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Research works printed but not linked: 31

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Metadata

Authors
Guimond, S., Maccarana, M., Olwin, B. B., Lindahl, U., & Rapraeger, A. C.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1993-11
Volume
268
Issue
32
Pages
23906-23914
ISSN
0021-9258
DOI
10.1016/s0021-9258(20)80471-2
Cited by
481
References
1
Language
en
Licence

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