|The low density lipoprotein receptor-related protein is a motogenic receptor for plasminogen activator inhibitor-1.|
|PMID: 15001579 Owner: NLM Status: MEDLINE|
|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.|
|Bernard Degryse; Jaap G Neels; Ralf-Peter Czekay; Kathleen Aertgeerts; Yu-Ichi Kamikubo; David J Loskutoff|
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|Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2004-03-04|
|Title: The Journal of biological chemistry Volume: 279 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2004 May|
|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|
|Languages: eng Pagination: 22595-604 Citation Subset: IM|
|Department of Cell Biology, The Scripps Research Institute, VB-3, La Jolla, California 92037, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Active Transport, Cell Nucleus
Cell Line, Tumor
Cell Membrane / metabolism
Cytoskeleton / metabolism
Dose-Response Relationship, Drug
LDL-Receptor Related Protein 1 / physiology*
Phosphotyrosine / chemistry
Plasminogen Activator Inhibitor 1 / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Surface Plasmon Resonance
Tyrosine / chemistry
|HL31950/HL/NHLBI NIH HHS|
|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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