Document Detail


Low density lipoprotein (LDL) receptor-related protein 1B impairs urokinase receptor regeneration on the cell surface and inhibits cell migration.
MedLine Citation:
PMID:  12194987     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The low density lipoprotein (LDL) receptor-related protein 1B (LRP1B) is a newly identified member of the LDL receptor family and is closely related to LRP. It was discovered as a putative tumor suppressor and is frequently inactivated in lung cancer cells. In the present study, we used an LRP1B minireceptor (mLRP1B4), which mimics the function and trafficking of LRP1B, to explore the roles of LRP1B on the plasminogen activation system. We found that mLRP1B4 and urokinase plasminogen activator receptor (uPAR) form immunoprecipitable complexes on the cell surface in the presence of complexes of uPA and its inhibitor, plasminogen activator inhibitor type-1 (PAI-1). However, compared with cells expressing the analogous LRP minireceptor (mLRP4), cells expressing mLRP1B4 display a substantially slower rate of uPA.PAI-1 complex internalization. Expression of mLRP1B4, or an mLRP4 mutant deficient in endocytosis, leads to an accumulation of uPAR at the cell surface and increased cell-associated uPA and PAI-1 when compared with cells expressing mLRP4. In addition, we found that expression of mLRP1B or the mLRP4 endocytosis mutant impairs the regeneration of unoccupied uPAR on the cell surface and that this correlates with a diminished rate of cell migration. Taken together, these results demonstrate that LRP1B can function as a negative regulator of uPAR regeneration and cell migration.
Authors:
Yonghe Li; Jane M Knisely; Wenyan Lu; Lynn M McCormick; Jieyi Wang; Jack Henkin; Alan L Schwartz; Guojun Bu
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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:  2002-08-22
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  277     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-10-28     Completed Date:  2003-01-17     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  42366-71     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, Missouri 63110, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
CHO Cells
Cell Movement
Cricetinae
Plasminogen Activator Inhibitor 1 / metabolism
Receptors, Cell Surface / metabolism*
Receptors, LDL / metabolism*
Receptors, Urokinase Plasminogen Activator
Urokinase-Type Plasminogen Activator / metabolism
Chemical
Reg. No./Substance:
0/LRP1B protein, human; 0/Lrp4 protein, mouse; 0/Plasminogen Activator Inhibitor 1; 0/Plaur protein, mouse; 0/Receptors, Cell Surface; 0/Receptors, LDL; 0/Receptors, Urokinase Plasminogen Activator; EC 3.4.21.73/Urokinase-Type Plasminogen Activator

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