Document Detail


The low density lipoprotein receptor-related protein is a motogenic receptor for plasminogen activator inhibitor-1.
MedLine Citation:
PMID:  15001579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although plasminogen activator inhibitor-1 (PAI-1) is known to stimulate cell migration, little is known about underlying mechanisms. We show that both active and inactive (e.g. cleaved) PAI-1 can activate the Jak/Stat signaling system and stimulate cell migration in chemotaxis, haptotaxis, chemokinesis, and wound healing assays. Moreover, antibodies to the LDL receptor-related protein (LRP) and an LRP antagonist (RAP) blocked these motogenic effects of PAI-1, while a PAI-1 mutant that did not bind to LRP failed to activate the Jak/Stat signaling pathway or to stimulate cell migration. PAI-1 had no chemotactic effect on LRP-deficient cells. These results indicate that LRP is a signaling molecule, that it mediates the migration-promoting activity of PAI-1, and that this activity does not require intact, biologically active PAI-1. Activation of this LRP-dependent signaling pathway by PAI-1 may begin to explain how the inhibitor stimulates cell migration in a variety of normal and pathological processes.
Authors:
Bernard Degryse; Jaap G Neels; Ralf-Peter Czekay; Kathleen Aertgeerts; Yu-Ichi Kamikubo; David J Loskutoff
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-03-04
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-05-17     Completed Date:  2004-06-30     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  22595-604     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, The Scripps Research Institute, VB-3, La Jolla, California 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Actins / metabolism
Active Transport, Cell Nucleus
Blotting, Western
Cell Line
Cell Line, Tumor
Cell Membrane / metabolism
Cell Movement
Cells, Cultured
Chemotaxis
Cytoskeleton / metabolism
Dose-Response Relationship, Drug
Humans
Kinetics
LDL-Receptor Related Protein 1 / physiology*
Microscopy, Fluorescence
Mutation
Phosphotyrosine / chemistry
Plasminogen Activator Inhibitor 1 / metabolism*
Precipitin Tests
Protein Binding
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Surface Plasmon Resonance
Time Factors
Tyrosine / chemistry
Wound Healing
Grant Support
ID/Acronym/Agency:
HL31950/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Actins; 0/LDL-Receptor Related Protein 1; 0/Plasminogen Activator Inhibitor 1; 21820-51-9/Phosphotyrosine; 55520-40-6/Tyrosine

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


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