HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Quinn, K. A. Articles by Owensby, D. A. Search for Related Content PubMed PubMed Citation Articles by Quinn, K. A. Articles by Owensby, D. A. Social Bookmarking                      What's this?

Volume 272, Number 38, Issue of September 19, 1997 pp. 23946-23951
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Soluble Low Density Lipoprotein Receptor-related Protein (LRP) Circulates in Human Plasma

(Received for publication, March 17, 1997, and in revised form, June 9, 1997)

Kathryn A. Quinn , Philip G. Grimsley , Yang-Ping Dai , Michael Tapner ^§ , Colin N. Chesterman and Dwain A. Owensby ^¶

From the  Center for Thrombosis and Vascular Research, University of New South Wales, Sydney 2052, Australia, the ^§ Storr Liver Unit, Department of Medicine, University of Sydney at Westmead Hospital, Westmead 2145, Australia, and the ^¶ Illawarra Regional Hospital, Wollongong, New South Wales 2500, Australia

Our studies have identified a soluble molecule in normal human plasma and serum with the characteristics of the -chain of the low density lipoprotein receptor-related protein (LRP). LRP is a large multifunctional receptor mediating the clearance of diverse ligands, including selected lipoproteins, various protease inhibitor complexes, and thrombospondin. A soluble molecule (sLRP) has been isolated from plasma using an affinity matrix coupled with methylamine-activated ₂-macroglobulin, the ligand uniquely recognized by LRP, and eluted with EDTA. This eluate contains a protein that co-migrates on SDS-polyacrylamide gel electrophoresis with authentic human placental LRP -chain, is recognized by anti-LRP -chain monoclonal antibodies, and binds the 39-kDa receptor-associated protein (RAP) and tissue plasminogen activator-inhibitor complexes. A similar RAP-binding molecule was detected in medium conditioned for 24 h by primary cultures of rat hepatocytes, suggesting that the liver may be the in vivo source of sLRP. In contrast, immunoprecipitation experiments failed to detect the production of sLRP by cultured HepG2 hepatoma and primary human fibroblast cells. Addition of a soluble form of LRP to cultured HepG2 cells resulted in a significant inhibition of capacity of these cells to degrade tPA, a process that has been demonstrated to be mediated by cell surface LRP. Preliminary data indicate that the concentration of sLRP is altered in the plasma of patients with liver disease. Increased levels of sLRP may antagonize the clearance of ligands by cell bound LRP perturbing diverse processes including lipid metabolism, cell migration and extracellular proteinase activity.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				V. Montel, A. Gaultier, R. D. Lester, W. M. Campana, and S. L. Gonias The Low-Density Lipoprotein Receptor Related Protein Regulates Cancer Cell Survival and Metastasis Development Cancer Res., October 15, 2007; 67(20): 9817 - 9824. [Abstract] [Full Text] [PDF]

				R. Polavarapu, M. C. Gongora, H. Yi, S. Ranganthan, D. A. Lawrence, D. Strickland, and M. Yepes Tissue-type plasminogen activator-mediated shedding of astrocytic low-density lipoprotein receptor-related protein increases the permeability of the neurovascular unit Blood, April 15, 2007; 109(8): 3270 - 3278. [Abstract] [Full Text] [PDF]

				E. A. Williams, R. J. Ing, J. P. Hart, J. Jaggers, F. H. Kern, D. M. Craig, and S. V. Pizzo Soluble {alpha}2-macroglobulin receptor is increased in endotracheal aspirates from infants and children after cardiopulmonary bypass J. Thorac. Cardiovasc. Surg., May 1, 2005; 129(5): 1098 - 1103. [Abstract] [Full Text] [PDF]

				L. Anderson Candidate-based proteomics in the search for biomarkers of cardiovascular disease J. Physiol., February 15, 2005; 563(1): 23 - 60. [Abstract] [Full Text] [PDF]

				A. Kinoshita, T. Shah, M. M. Tangredi, D. K. Strickland, and B. T. Hyman The Intracellular Domain of the Low Density Lipoprotein Receptor-related Protein Modulates Transactivation Mediated by Amyloid Precursor Protein and Fe65 J. Biol. Chem., October 17, 2003; 278(42): 41182 - 41188. [Abstract] [Full Text] [PDF]

				J. Rohlena, J. A. Kolkman, R. C. Boertjes, K. Mertens, and P. J. Lenting Residues Phe342-Asn346 of Activated Coagulation Factor IX Contribute to the Interaction with Low Density Lipoprotein Receptor-related Protein J. Biol. Chem., March 7, 2003; 278(11): 9394 - 9401. [Abstract] [Full Text] [PDF]

				P. May, Y. K. Reddy, and J. Herz Proteolytic Processing of Low Density Lipoprotein Receptor-related Protein Mediates Regulated Release of Its Intracellular Domain J. Biol. Chem., May 17, 2002; 277(21): 18736 - 18743. [Abstract] [Full Text] [PDF]

				B. Berwin, J. P. Hart, S. V. Pizzo, and C. V. Nicchitta CD91-Independent Cross-Presentation of GRP94(gp96)-Associated Peptides J. Immunol., May 1, 2002; 168(9): 4282 - 4286. [Abstract] [Full Text] [PDF]

				C. H. Redfern, M. Y. Degtyarev, A. T. Kwa, N. Salomonis, N. Cotte, T. Nanevicz, N. Fidelman, K. Desai, K. Vranizan, E. K. Lee, et al. Conditional expression of a Gi-coupled receptor causes ventricular conduction delay and a lethal cardiomyopathy PNAS, April 25, 2000; 97(9): 4826 - 4831. [Abstract] [Full Text] [PDF]

				J. Laukkanen, P. Lehtolainen, P. J. Gough, D. R. Greaves, S. Gordon, and S. Yla-Herttuala Adenovirus-Mediated Gene Transfer of a Secreted Form of Human Macrophage Scavenger Receptor Inhibits Modified Low-Density Lipoprotein Degradation and Foam-Cell Formation in Macrophages Circulation, March 14, 2000; 101(10): 1091 - 1096. [Abstract] [Full Text] [PDF]

				W Hampe, J Urny, I Franke, S. Hoffmeister-Ullerich, D Herrmann, C. Petersen, J Lohmann, and H. Schaller A head-activator binding protein is present in hydra in a soluble and a membrane-anchored form Development, January 9, 1999; 126(18): 4077 - 4086. [Abstract] [PDF]

				T. C. Marlovits, C. Abrahamsberg, and D. Blaas Very-Low-Density Lipoprotein Receptor Fragment Shed from HeLa Cells Inhibits Human Rhinovirus Infection J. Virol., December 1, 1998; 72(12): 10246 - 10250. [Abstract] [Full Text] [PDF]

				K. W. S. Ko, R. S. McLeod, R. K. Avramoglu, J. Nimpf, D. J. FitzGerald, J. Vukmirica, and Z. Yao Mutation at the Processing Site of Chicken Low Density Lipoprotein Receptor-related Protein Impairs Efficient Endoplasmic Reticulum Exit, but Proteolytic Cleavage Is Not Essential for Its Endocytic Functions J. Biol. Chem., October 23, 1998; 273(43): 27779 - 27785. [Abstract] [Full Text] [PDF]