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

J. Biol. Chem., Vol. 277, Issue 4, 2511-2516, January 25, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/4/2511    most recent M102293200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Westein, E. Articles by Lenting, P. J. Search for Related Content PubMed PubMed Citation Articles by Westein, E. Articles by Lenting, P. J. Social Bookmarking                      What's this?

The -Chains of C4b-binding Protein Mediate Complex Formation with Low Density Lipoprotein Receptor-related Protein^*

Erik Westein, Cécile V. Denis^§, Bonno N. Bouma, and Peter J. Lenting^¶

From the  Laboratory for Thrombosis and Haemostasis, Department of Haematology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands and ^§ INSERM U143, Hôpital Bicêtre, 94276 le Kremlin-Bicêtre, France

C4b-binding protein (C4BP) is a heparin-binding protein that participates in both the complement and hemostatic system. We investigated the interaction between C4BP and low density lipoprotein receptor-related protein (LRP), an endocytic receptor involved in the catabolism of various heparin-binding proteins. Both plasma-derived C4BP and recombinant C4BP consisting of only its -chains (rC4BP) bound efficiently to immobilized LRP, as determined by surface plasmon resonance analysis. Complementary, two distinct fragments of LRP, i.e. clusters II and IV, both associated to immobilized rC4BP, and binding could be inhibited by the LRP antagonist receptor-associated protein. Further analysis showed that association of rC4BP to LRP was inhibited by heparin or by anti-C4BP antibody RU-3B9, which recognizes the heparin-binding region of the C4BP -chains. In cellular degradation experiments, LRP-expressing fibroblasts effectively degraded ¹²⁵I-labeled rC4BP, whereas their LRP-deficient counterparts displayed a 4-fold diminished capacity of degrading ¹²⁵I-rC4BP. Finally, initial clearance of C4BP in mice was significantly delayed upon co-injection with receptor-associated protein. In conclusion, our data demonstrate that the -chains of C4BP comprise a binding site for LRP. We propose that LRP mediates at least in part the catabolism of C4BP and, as such, may regulate C4BP participation in complement and hemostatic processes.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				C. V. Denis, S. J. Roberts, T. M. Hackeng, and P. J. Lenting In Vivo Clearance of Human Protein S in a Mouse Model: Influence of C4b-Binding Protein and the Heerlen Polymorphism Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2209 - 2215. [Abstract] [Full Text] [PDF]

				M. I. Nonaka, Y. Hishikawa, N. Moriyama, T. Koji, R. T. Ogata, A. Kudo, H. Kawakami, and M. Nonaka Complement C4b-Binding Protein as a Novel Murine Epididymal Secretory Protein Biol Reprod, December 1, 2003; 69(6): 1931 - 1939. [Abstract] [Full Text] [PDF]

				L. C. Kao, A. Germeyer, S. Tulac, S. Lobo, J. P. Yang, R. N. Taylor, K. Osteen, B. A. Lessey, and L. C. Giudice Expression Profiling of Endometrium from Women with Endometriosis Reveals Candidate Genes for Disease-Based Implantation Failure and Infertility Endocrinology, July 1, 2003; 144(7): 2870 - 2881. [Abstract] [Full Text] [PDF]