Document Detail


The GM2 activator protein, a novel inhibitor of platelet-activating factor.
MedLine Citation:
PMID:  10329374     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The GM2 activator protein is required as a substrate-specific cofactor for beta-hexosaminidase A to hydrolyze GM2 ganglioside. The GM2 activator protein reversibly binds and solubilizes individual GM2 ganglioside molecules, making them available as substrate. Although GM2 ganglioside is the strongest binding ligand for the activator protein, it can also bind and transport between membranes a series of other glycolipids, even at neutral pH. Biosynthetic studies have shown that a large portion of newly synthesized GM2 activator molecules are not targeted to the lysosome, but are secreted and can then be recaptured by other cells through a carbohydrate independent mechanism. Thus, the GM2 activator protein may have other in vivo functions. We found that the GM2 activator protein can inhibit, through specific binding, the ability of platelet activating factor (PAF) to stimulate the release of intracellular Ca2+ pools by human neutrophils. PAF is a biologically potent phosphoacylglycerol. Inhibitors for PAF's role in the pathogenesis of inflammatory bowel disease and asthma have been sought as potential therapeutic agents. The inherent stability and protease resistance of the small, monomeric GM2 activator protein, coupled with the ability to produce large quantities of the functional protein in transformed bacteria, suggest it may serve as such an agent.
Authors:
B Rigat; D Reynaud; N Smiljanic-Georgijev; D Mahuran
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  258     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  1999 May 
Date Detail:
Created Date:  1999-06-15     Completed Date:  1999-06-15     Revised Date:  2010-07-06    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  256-9     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Academic Press.
Affiliation:
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Calcium / metabolism
G(M2) Activator Protein
Humans
Platelet Activating Factor / antagonists & inhibitors*,  metabolism
Protein Binding
Proteins / metabolism*
Spectrometry, Fluorescence
Grant Support
ID/Acronym/Agency:
10435//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/G(M2) Activator Protein; 0/Platelet Activating Factor; 0/Proteins; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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