NDLI: Low Density Lipoprotein (LDL) Receptor-related Protein 1B Impairs Urokinase Receptor Regeneration on the Cell Surface and Inhibits Cell Migration

Content Provider	Journal of Biological Chemistry (JBC)
Author	Li, Yonghe Knisely, Jane M. Lu, Wenyan McCormick, Lynn M. Wang, Jieyi Henkin, Jack Schwartz, Alan L. Bu, Guojun
Abstract	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.
Related Links	http://www.jbc.org/content/277/44/42366.abstract
Ending Page	42371
Starting Page	42366
Page Count	6
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	44
Volume Number	277
DOI	10.1074/jbc.M207705200
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2002-11-01
Access Restriction	Open
Subject Keyword	Urokinase plasminogen activator (uPA) UPA receptor (uPAR) UPA amino-terminal fragment (ATF) Single chain urokinase (scuPA) Low density lipoprotein receptor (LDLR) Low density lipoprotein receptor-related protein (LRP) MiniLRP (mLRP) Plasminogen activator inhibitor type-1 (PAI-1) Chinese hamster ovary (CHO) 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS) Hemagglutinin (HA) Mutant (Mu) MOLECULAR BASIS OF CELL AND DEVELOPMENTAL BIOLOGY
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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