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Heparan sulfates mediate the binding of basic fibroblast growth factor to a specific receptor on neural precursor cells

Citation

Brickman, YG and Ford, MD and Small, DH and Bartlett, PF and Nurcombe, V, Heparan sulfates mediate the binding of basic fibroblast growth factor to a specific receptor on neural precursor cells, Journal of Biological Chemistry, 270, (42) pp. 24941-24948. ISSN 0021-9258 (1995) [Refereed Article]


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Copyright Statement

Copyright 1995 The American Society for Biochemistry and Molecular Biology, Inc.

Official URL: http://www.jbc.org/content/270/42/24941.abstract

DOI: doi:10.1074/jbc.270.42.24941

Abstract

Heparan sulfate proteoglycans are thought to be obligatory for receptor binding and subsequent mitogenic activity of basic fibroblast growth factor (FGF-2). In a previous study (Nurcombe V., Ford, M. D., Wildschut, J., Bartlett, P. F. (1993) Science 260, 103-106) we have shown that primary cultures of mouse neuroepithelial cells and a cell line derived from them, 2.3D, secrete a heparan sulfate proteoglycan with a high affinity for FGF-2. In this study, a combination of affinity chromatography and gel chromatography was used to further isolate heparan sulfate side chains with high affinity for FGF-2. These active chains had an average molecular weight of 18,000-20,000. In order to determine whether heparan sulfate chains with specificity for FGF-2 also displayed selectivity for the different FGF receptors, peptides designed to the heparin-binding region of the receptors were used in competitive inhibition studies. The structure of the predicted heparin-binding domain of the FGF receptor 1 was modeled on the basis of its presumed secondary and tertiary structure homology with immunoglobulin loops. These results suggested that many of the basic residues within the second immunoglobulin loop of the FGF receptor 1 form a basic domain in the molecule and therefore form part of a heparin-binding site. Peptides homologous to this region of FGF receptor 1 were shown to inhibit mitogenesis in 2.3D cells, while those to FGF receptor types 2, 3, and 4 did not. A reverse transcriptase-polymerase chain reaction assay designed to detect expression of the four FGF receptors types demonstrated that FGF receptors 1 and 3 were present on the 2.3D cell line but that receptors 2 and 4 were not. These findings indicate that unique heparan sulfate domains interact with specific cell-surface receptors to direct cellular responses.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Small, DH (Professor David Small)
ID Code:75423
Year Published:1995
Web of Science® Times Cited:80
Deposited By:Research Division
Deposited On:2012-01-30
Last Modified:2012-06-26
Downloads:0

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