Document Detail


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.
MedLine Citation:
PMID:  12626395     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Steven M Rickard; Rosemary S Mummery; Barbara Mulloy; Christopher C Rider
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-02-06
Journal Detail:
Title:  Glycobiology     Volume:  13     ISSN:  0959-6658     ISO Abbreviation:  Glycobiology     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-05-07     Completed Date:  2004-01-05     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9104124     Medline TA:  Glycobiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  419-26     Citation Subset:  IM    
Affiliation:
School of Biological Sciences, Royal Holloway University of London, Egham Hill, Egham, Surrey TW20 0EX, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
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:
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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