|
Originally published In Press as doi:10.1074/jbc.M508148200 on August 15, 2005
J. Biol. Chem., Vol. 280, Issue 44, 36873-36882, November 4, 2005
Two Functional Active Conformations of the Integrin 2 1, Depending on Activation Condition and Cell Type*
Gerlinde R. Van de Walle ,
Karen Vanhoorelbeke 1,
Zsuzsa Majer ,
Eszter Illyés ,
Johan Baert¶,
Inge Pareyn , and
Hans Deckmyn 2
From the
Laboratories for Thrombosis Research and ¶Histology, Interdisciplinary Research Centre, Katholieke Universiteit Leuven, Campus Kortrijk, 8500 Kortrijk, Belgium and the Department of Organic Chemistry, Eötvös Loránd University, 1518 Budapest, Hungary
For several integrins, the existence of multiple conformational states has been studied intensively. For the integrin 2 1, a major collagen receptor on platelets and other cell types, however, no such experimental data were available thus far. Recently, our group has developed a monoclonal antibody IAC-1 sensitive to the molecular conformation of 2 1 because it only binds to the activated state of 2 1 on platelets, induced upon inside-out signaling. By investigating IAC-1 binding in combination with collagen binding after inside-out stimulation and outside manipulation, we demonstrated the existence of three different conformations of 2 1 on platelets and Chinese hamster ovary cells as follows: (i) a nonactivated, resting state with no collagen nor IAC-1 binding; (ii) an intermediate state, induced by outside manipulation, with collagen but no IAC-1 binding; and (iii) a fully activated state, induced after inside-out stimulation, with both collagen and IAC-1 binding. Moreover, these different conformational states of 2 1 are dependent on the cell type where 2 1 is expressed, as IAC-1 binding to peripheral blood mononuclear cells and Jurkat cells could also be induced by outside manipulation, in contrast to platelets and 2 1-expressing Chinese hamster ovary cells. Finally, we revealed a functional relevance for these different conformational states because the conformation of 2 1, induced after outside manipulation, resulted in significantly more cell spreading on coated collagen compared with nonactivated or inside-out stimulated cells.
Received for publication, July 26, 2005
* This work was supported by Grant GOA/2004/09 from the Katholieke Universiteit Leuven, the Hungarian Research Fund/OTKA Grant T037719, and a Bilateral Collaboration Grant BIL/04/36. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Postdoctoral fellow of the Fonds voor Wetenschappelijk Onderzoek Vlaanderen.
2 To whom correspondence should be addressed: Laboratory for Thrombosis Research, Interdisciplinary Research Centre, Katholieke Universiteit Leuven, Campus Kortrijk, E. Sabbelaan 53, 8500 Kortrijk, Belgium. Tel.: 32-56246422; Fax: 32-56246997; E-mail: Hans.deckmyn{at}kulak.ac.be.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
D. Varga-Szabo, I. Pleines, and B. Nieswandt
Cell Adhesion Mechanisms in Platelets
Arterioscler. Thromb. Vasc. Biol.,
March 1, 2008;
28(3):
403 - 412.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. L. Connors, J. Jokinen, D. J. White, J. S. Puranen, P. Kankaanpaa, P. Upla, M. Tulla, M. S. Johnson, and J. Heino
Two Synergistic Activation Mechanisms of {alpha}2beta1 Integrin-mediated Collagen Binding
J. Biol. Chem.,
May 11, 2007;
282(19):
14675 - 14683.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Bix, R. A. Iozzo, B. Woodall, M. Burrows, A. McQuillan, S. Campbell, G. B. Fields, and R. V. Iozzo
Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the {alpha}2{beta}1-integrin receptor
Blood,
May 1, 2007;
109(9):
3745 - 3748.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. R. Van de Walle, A. Schoolmeester, B. F. Iserbyt, J. M. E. M. Cosemans, J. W. M. Heemskerk, M. F. Hoylaerts, A. Nurden, K. Vanhoorelbeke, and H. Deckmyn
Activation of {alpha}IIb{beta}3 is a sufficient but also an imperative prerequisite for activation of {alpha}2{beta}1 on platelets
Blood,
January 15, 2007;
109(2):
595 - 602.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Bix, R. Castello, M. Burrows, J. J. Zoeller, M. Weech, R. A. Iozzo, C. Cardi, M. L. Thakur, C. A. Barker, K. Camphausen, et al.
Endorepellin In Vivo: Targeting the Tumor Vasculature and Retarding Cancer Growth and Metabolism.
J Natl Cancer Inst,
November 15, 2006;
98(22):
1634 - 1646.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. W. Orr, M. H. Ginsberg, S. J. Shattil, H. Deckmyn, and M. A. Schwartz
Matrix-specific Suppression of Integrin Activation in Shear Stress Signaling
Mol. Biol. Cell,
November 1, 2006;
17(11):
4686 - 4697.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z.-G. Zhang, I. Bothe, F. Hirche, M. Zweers, D. Gullberg, G. Pfitzer, T. Krieg, B. Eckes, and M. Aumailley
Interactions of primary fibroblasts and keratinocytes with extracellular matrix proteins: contribution of {alpha}2{beta}1 integrin.
J. Cell Sci.,
May 1, 2006;
119(Pt 9):
1886 - 1895.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|