NDLI: Control of Growth Factor Networks by Heparan Sulfate Proteoglycans

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Control of Growth Factor Networks by Heparan Sulfate Proteoglycans

Content Provider	Springer Nature Link
Author	Forsten Williams, Kimberly Chu, Chia Lin Fann, Michael Buczek Thomas, Jo Ann Nugent, Matthew A.
Copyright Year	2008
Abstract	Growth factor binding to transmembrane protein receptors is generally understood to initiate cell signaling. Receptor binding of heparin-binding growth factors (HB-GFs), such as fibroblast growth factor-2 (FGF-2), is regulated by interactions with heparan sulfate proteoglycans. While there is some specificity for binding to heparan sulfate, overlap in sites for different growth factors may allow for cross regulation. Here we demonstrate, using experiments and computer simulations, that the HB-GFs FGF-2 and heparin-binding EGF-like growth factor (HB-EGF) can cross regulate receptor binding of the other despite having unique receptors. The ability of HSPG to stabilize HB-GF receptor binding is critical for competing growth factors to modulate receptor binding with both enhanced and reduced binding possible depending on this stabilization process. HSPG density and affinity for HB-GF are also critical factors for HB-GF cross regulation. Simulations further reveal that HB-GF can regulate receptor binding of non-HB-GFs such as EGF even when the two proteins share no binding sites when other HB-GF are present within the network. Proliferation studies demonstrate potentiation of HB-EGF-induced growth by FGF-2 indicating that competition networks can alter biological response. Exogenous manipulation of cellular responses to growth factors in complex living systems will require understanding the HSPG-controlled network.
Starting Page	2134
Ending Page	2148
Page Count	15
File Format	PDF
ISSN	00906964
Journal	Annals of Biomedical Engineering
Volume Number	36
Issue Number	12
e-ISSN	15739686
Language	English
Publisher	Springer US
Publisher Date	2008-10-07
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Receptors Heparin Fibroblast growth factor-2 Heparin-binding-EGF-like growth factor Binding Epidermal growth factor Network Growth factor Biochemistry Mechanics Biophysics/Biomedical Physics Biomedical Engineering Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Biomedical Engineering

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Control of Growth Factor Networks by Heparan Sulfate Proteoglycans

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