|
Originally published In Press as doi:10.1074/jbc.M211566200 on December 22, 2002
J. Biol. Chem., Vol. 278, Issue 9, 7099-7107, February 28, 2003
Lipid Raft-dependent and -independent Signaling
through HLA-DR Molecules*
Marlène
Bouillon ,
Youssef
El
Fakhry ,
Julie
Girouard ,
Hayssam
Khalil§¶,
Jacques
Thibodeau§ , and
Walid
Mourad **
From the Centre de Recherche en Rhumatologie et
Immunologie, (CHUL), Département de Médecine,
Université Laval, Quebec City, Quebec G1V 4G2, Canada and the
§ Laboratoire d'Immunologie Moléculaire,
Département de Microbiologie et Immunologie, Faculté de
Médecine, Université de Montréal, Montreal, Quebec
H3C 3J7, Canada
Lipid rafts are plasma membrane microdomains that
are highly enriched in signaling molecules and that act as signal
transduction platforms for many immune receptors. The
involvement of these microdomains in HLA-DR-induced signaling is less
well defined. We examined the constitutive presence of HLA-DR molecules
in lipid rafts, their possible recruitment into these microdomains, and the role of these microdomains in HLA-DR-induced responses. We detected significant amounts of HLA-DR molecules in the lipid rafts of
EBV+ and EBV B cell lines, monocytic
cell lines, transfected HeLa cells, tonsillar B cells, and human
monocytes. Localization of HLA-DR in these microdomains was unaffected
by the deletion of the cytoplasmic domain of both the and chains. Ligation of HLA-DR with a bivalent, but not a monovalent,
ligand resulted in rapid tyrosine phosphorylation of many substrates,
especially Lyn, and activation of ERK1/2 MAP kinase. However, the
treatment failed to induce further recruitment of HLA-DR molecules into
lipid rafts. The HLA-DR-induced signaling events were accompanied by
the induction of cell-cell adhesion that could be inhibited by PTK and
Lyn but not ERK1/2 inhibitors. Disruption of lipid rafts by
methyl- -cyclodextrin (M CD) resulted in the loss of membrane raft
association with HLA-DR molecules, inhibition of HLA-DR-mediated
protein tyrosine phosphorylation and cell-cell adhesion. M CD
did not affect the activation of ERK1/2, which was absent from lipid
rafts. These results indicate that although all the HLA-DR-induced
events studied are dependent on HLA-DR dimerization, some require the
presence of HLA-DR molecules in lipid rafts, whereas others do not.
*
This work was supported by grants from CIHR, the
Arthritis Society of Canada, and the Canadian Arthritis Network.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
¶
Recipient of a Formation Chercheurs & Aide Recherche studentship.
Recipient of a Canadian Institutes for Health Research scholarship.
**
Recipient of a scientist award from the Arthritis Society of
Canada. To whom correspondence should be addressed: Centre de Recherche
en Rhumatologie et Immunologie, CHUL, 2705 boulevard Laurier, T1-49,
Quebec City, Quebec G1V 4G2, Canada. Tel.: 418-654-2772; Fax:
418-654-2765; E-mail: Walid.Mourad@crchul.ulaval.ca.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

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

|
 |

|
 |
 
R. Knorr, C. Karacsonyi, and R. Lindner
Endocytosis of MHC molecules by distinct membrane rafts
J. Cell Sci.,
May 15, 2009;
122(10):
1584 - 1594.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Sasseville, M.-C. Gagnon, C. Guillemette, R. Sullivan, R. B. Gilchrist, and F. J. Richard
Regulation of Gap Junctions in Porcine Cumulus-Oocyte Complexes: Contributions of Granulosa Cell Contact, Gonadotropins, and Lipid Rafts
Mol. Endocrinol.,
May 1, 2009;
23(5):
700 - 710.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Girouard, G. Frenette, and R. Sullivan
Compartmentalization of Proteins in Epididymosomes Coordinates the Association of Epididymal Proteins with the Different Functional Structures of Bovine Spermatozoa
Biol Reprod,
May 1, 2009;
80(5):
965 - 972.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Sasseville, N. Cote, M.-C. Gagnon, and F. J. Richard
Up-Regulation of 3'5'-Cyclic Guanosine Monophosphate-Specific Phosphodiesterase in the Porcine Cumulus-Oocyte Complex Affects Steroidogenesis during in Vitro Maturation
Endocrinology,
November 1, 2008;
149(11):
5568 - 5576.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Girouard, G. Frenette, and R. Sullivan
Seminal Plasma Proteins Regulate the Association of Lipids and Proteins Within Detergent-Resistant Membrane Domains of Bovine Spermatozoa
Biol Reprod,
May 1, 2008;
78(5):
921 - 931.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. A. Kriegel, S. Adam-Klages, C. Gabler, N. Blank, M. Schiller, C. Scheidig, J. R. Kalden, and H.-M. Lorenz
Anti-HLA-DR-triggered monocytes mediate in vitro T cell anergy
Int. Immunol.,
April 1, 2008;
20(4):
601 - 613.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Sloma, M.-T. Zilber, T. Vasselon, N. Setterblad, M. Cavallari, L. Mori, G. De Libero, D. Charron, N. Mooney, and C. Gelin
Regulation of CD1a Surface Expression and Antigen Presentation by Invariant Chain and Lipid Rafts
J. Immunol.,
January 15, 2008;
180(2):
980 - 987.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Reyes-Moreno, E. Sharif-Askari, J. Girouard, C. Leveille, M. Jundi, A. Akoum, R. Lapointe, A. Darveau, and W. Mourad
Requirement of Oxidation-dependent CD40 Homodimers for CD154/CD40 Bidirectional Signaling
J. Biol. Chem.,
July 6, 2007;
282(27):
19473 - 19480.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Karacsonyi, T. Bedke, N. Hinrichsen, R. Schwinzer, and R. Lindner
MHC II molecules and invariant chain reside in membranes distinct from conventional lipid rafts
J. Leukoc. Biol.,
November 1, 2005;
78(5):
1097 - 1105.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M.-T. Zilber, N. Setterblad, T. Vasselon, C. Doliger, D. Charron, N. Mooney, and C. Gelin
MHC class II/CD38/CD9: a lipid-raft-dependent signaling complex in human monocytes
Blood,
November 1, 2005;
106(9):
3074 - 3081.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. J. Poloso, A. Muntasell, and P. A. Roche
MHC Class II Molecules Traffic into Lipid Rafts during Intracellular Transport
J. Immunol.,
October 1, 2004;
173(7):
4539 - 4546.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Karacsonyi, R. Knorr, A. Fulbier, and R. Lindner
Association of Major Histocompatibility Complex II with Cholesterol- and Sphingolipid-rich Membranes Precedes Peptide Loading
J. Biol. Chem.,
August 13, 2004;
279(33):
34818 - 34826.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. El Fakhry, M. Bouillon, C. Leveille, A. Brunet, H. Khalil, J. Thibodeau, and W. Mourad
Delineation of the HLA-DR Region and the Residues Involved in the Association with the Cytoskeleton
J. Biol. Chem.,
April 30, 2004;
279(18):
18472 - 18480.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. P. Mone, P. Huang, H. Pelicano, C. M. Cheney, J. M. Green, J. Y. Tso, A. J. Johnson, S. Jefferson, T. S. Lin, and J. C. Byrd
Hu1D10 induces apoptosis concurrent with activation of the AKT survival pathway in human chronic lymphocytic leukemia cells
Blood,
March 1, 2004;
103(5):
1846 - 1854.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. P. Dolan, T. P. Phelan, D. Ilkovitch, L. Qi, W. F. Wade, T. M. Laufer, and S. Ostrand-Rosenberg
Invariant Chain and the MHC Class II Cytoplasmic Domains Regulate Localization of MHC Class II Molecules to Lipid Rafts in Tumor Cell-Based Vaccines
J. Immunol.,
January 15, 2004;
172(2):
907 - 914.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. B. Katzman and R. Longnecker
Cholesterol-dependent infection of Burkitt's lymphoma cell lines by Epstein-Barr virus
J. Gen. Virol.,
November 1, 2003;
84(11):
2987 - 2992.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|