JCB logo
HYBRIGENICS
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 23 June 2003. doi:10.1083/jcb.200302069
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow Correction (v162,p521)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Orr, A. W.
Right arrow Articles by Murphy-Ullrich, J. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Orr, A. W.
Right arrow Articles by Murphy-Ullrich, J. E.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0021-9525/2003/6/1179 $5.00
The Journal of Cell Biology, Volume 161, Number 6, 1179-1189

Article

 Low density lipoprotein receptor–related protein is a calreticulin coreceptor that signals focal adhesion disassembly

Anthony Wayne Orr1, Claudio E. Pedraza1, Manuel Antonio Pallero1, Carrie A. Elzie1, Silvia Goicoechea1, Dudley K. Strickland2 and Joanne E. Murphy-Ullrich1

1 Department of Pathology, Division of Molecular and Cellular Pathology and the Cell Adhesion and Matrix Research Center, University of Alabama at Birmingham, Birmingham, AL 35294
2 Department of Vascular Biology, Holland Laboratory, American Red Cross, Rockville, MD 20855

Address correspondence to Joanne E. Murphy-Ullrich, Dept. of Pathology and The Cell Adhesion and Matrix Research Center, University of Alabama at Birmingham, VH 668 1530, 3rd Ave. South, Birmingham, AL 35294-0019. Tel.: (205) 934-0415. Fax: (205) 975-934. E-mail: Murphy{at}path.uab.edu

Thrombospondin (TSP) signals focal adhesion disassembly (the intermediate adhesive state) through interactions with cell surface calreticulin (CRT). TSP or a peptide (hep I) of the active site induces focal adhesion disassembly through binding to CRT, which activates phosphoinositide 3-kinase (PI3K) and extracellular signal–related kinase (ERK) through G{alpha}i2 proteins. Because CRT is not a transmembrane protein, it is likely that CRT signals as part of a coreceptor complex. We now show that low density lipoprotein receptor–related protein (LRP) mediates focal adhesion disassembly initiated by TSP binding to CRT. LRP antagonists (antibodies, receptor-associated protein) block hep I/TSP-induced focal adhesion disassembly. LRP is necessary for TSP/hep I signaling because TSP/hep I is unable to stimulate focal adhesion disassembly or ERK or PI3K signaling in fibroblasts deficient in LRP. LRP is important in TSP–CRT signaling, as shown by the ability of hep I to stimulate association of G{alpha}i2 with LRP. The isolated proteins LRP and CRT interact, and LRP and CRT are associated with hep I in molecular complexes extracted from cells. These data establish a mechanism of cell surface CRT signaling through its coreceptor, LRP, and suggest a novel function for LRP in regulating cell adhesion.

Key Words: thrombospondin; G proteins; ERK; focal adhesions; cell adhesion

* Abbreviations used in this paper: {alpha}2M, {alpha}2-macroglobulin; BAE, bovine aortic endothelial; CRT, calreticulin; ERK, extracellular signal–related kinase; LRP, low density lipoprotein receptor–related protein; MEF, mouse embryonic fibroblast; PI3K, phosphoinositide 3 kinase; PTX, pertussis toxin; RAP, receptor-associated protein; TSP, thrombospondin.


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


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents