The low density lipoprotein receptor-related protein is a motogenic receptor for plasminogen activator inhibitor-1.

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.
Mesh Terms:
Actins, Active Transport, Cell Nucleus, Blotting, Western, Cell Line, Cell Line, Tumor, Cell Membrane, Cell Movement, Cells, Cultured, Chemotaxis, Cytoskeleton, Dose-Response Relationship, Drug, Humans, Kinetics, LDL-Receptor Related Protein 1, Microscopy, Fluorescence, Mutation, Phosphotyrosine, Plasminogen Activator Inhibitor 1, Precipitin Tests, Protein Binding, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Surface Plasmon Resonance, Time Factors, Tyrosine, Wound Healing
J. Biol. Chem.
Date: May. 21, 2004
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