| The binding of human glial cell line-derived neurotrophic factor to heparin and heparan sulfate: importance of 2-O-sulfate groups and effect on its interaction with its receptor, GFRalpha1. | |
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MedLine Citation:
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PMID: 12626395 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We report ELISA studies of the glycosaminoglycan binding properties of recombinant human glial cell line-derived neurotrophic factor (GDNF). We demonstrate relatively high affinity binding as soluble heparin competes with an IC50 of 0.1 micro g/ml. The binding of GDNF to heparin is particularly dependent on the presence of 2-O-sulfate groups. Highly sulfated heparan sulfate is also an effective competitor for GDNF binding. We also show that heparin at low concentrations protects GDNF from proteolytic modification by an endoprotease and also promotes the binding of GDNF to its receptor polypeptide, GFRalpha1. In both of these actions, 2-O-desulfated heparin is less effective. Considered overall, these findings provide strong support for a hypothesis that the bioactivity of GDNF during prenatal development is essentially dependent on the binding of this growth factor to 2-O-sulfate-rich heparin-related glycosaminoglycan. |
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Authors:
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Steven M Rickard; Rosemary S Mummery; Barbara Mulloy; Christopher C Rider |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-02-06 |
Journal Detail:
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Title: Glycobiology Volume: 13 ISSN: 0959-6658 ISO Abbreviation: Glycobiology Publication Date: 2003 Jun |
Date Detail:
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Created Date: 2003-05-07 Completed Date: 2004-01-05 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9104124 Medline TA: Glycobiology Country: England |
Other Details:
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Languages: eng Pagination: 419-26 Citation Subset: IM |
Affiliation:
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School of Biological Sciences, Royal Holloway University of London, Egham Hill, Egham, Surrey TW20 0EX, United Kingdom. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Binding Sites Cell Line Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Glial Cell Line-Derived Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor Receptors Heparin / chemistry, metabolism* Heparitin Sulfate / chemistry, metabolism* Humans Inhibitory Concentration 50 Magnetic Resonance Spectroscopy Nerve Growth Factors / antagonists & inhibitors, metabolism* Neuroglia / metabolism* Protein Binding Proto-Oncogene Proteins / metabolism* Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases / metabolism* Sulfates / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/GDNF protein, human; 0/GFRA1 protein, human; 0/Glial Cell Line-Derived Neurotrophic Factor; 0/Glial Cell Line-Derived Neurotrophic Factor Receptors; 0/Nerve Growth Factors; 0/Proto-Oncogene Proteins; 0/Sulfates; 9005-49-6/Heparin; 9050-30-0/Heparitin Sulfate; EC 2.7.10.1/Proto-Oncogene Proteins c-ret; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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