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*
Centre Nationale de la Recherche Scientifique, Unité Propre de Recherche 0415, Institut Cochin de Génétique Moléculaire, Paris, France; and
Institute of Ophthalmology, University College London, London, United Kingdom
Endothelium of the cerebral blood vessels, which constitutes the blood-brain barrier, controls leukocyte adhesion and trafficking to the brain. Investigating signaling pathways triggered by the engagement of adhesion molecules expressed on brain endothelial cells, we report here that ICAM-1 cross-linking induces tyrosine phosphorylation of three cytoskeleton-associated proteins: focal adhesion kinase, paxillin, and p130Cas (Cas), which are found to associate as complexes. Tyrosine-phosphorylated Cas associates with the adaptor protein Crk and the GTP exchange factor C3G. In the same conditions the small G protein Rho was activated, as shown by the increase in its GTP loading. In addition, tyrosine phosphorylation of focal adhesion kinase, paxillin, and Cas as well as triggering of the Crk signaling pathway are blocked by pretreatment of the cells with the exoenzyme C3, a specific Rho inhibitor. C3-sensitive activation of the c-Jun N-terminal kinase in response to ICAM-1 cross-linking is also observed, whereas no significant activation of Ras or of the extracellular signal-regulated kinase was detected. In conclusion, these results suggest that through coupling to Rho activation and phosphorylation of cytoskeletal proteins and transcription factors, ICAM-1 cross-linking participates in the cell shape changes and gene regulation that may accompany lymphocyte migration through the blood-brain barrier.
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S. J. Lee, K. Drabik, N. J. Van Wagoner, S. Lee, C. Choi, Y. Dong, and E. N. Benveniste ICAM-1-Induced Expression of Proinflammatory Cytokines in Astrocytes: Involvement of Extracellular Signal-Regulated Kinase and p38 Mitogen-Activated Protein Kinase Pathways J. Immunol., October 15, 2000; 165(8): 4658 - 4666. [Abstract] [Full Text] [PDF]
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S. Etienne-Manneville, J.-B. Manneville, P. Adamson, B. Wilbourn, J. Greenwood, and P.-O. Couraud ICAM-1-Coupled Cytoskeletal Rearrangements and Transendothelial Lymphocyte Migration Involve Intracellular Calcium Signaling in Brain Endothelial Cell Lines J. Immunol., September 15, 2000; 165(6): 3375 - 3383. [Abstract] [Full Text] [PDF]
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J. S. Alexander Rho, Tyrosine Kinase, Ca2+, and Junctions in Endothelial Hyperpermeability Circ. Res., August 18, 2000; 87(4): 268 - 271. [Full Text] [PDF]
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D. Mehta, D. D. Tang, M.-F. Wu, S. Atkinson, and S. J. Gunst Role of Rho in Ca2+-insensitive contraction and paxillin tyrosine phosphorylation in smooth muscle Am J Physiol Cell Physiol, August 1, 2000; 279(2): C308 - C318. [Abstract] [Full Text] [PDF]
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Q. Wang and C. M. Doerschuk Neutrophil-Induced Changes in the Biomechanical Properties of Endothelial Cells: Roles of ICAM-1 and Reactive Oxygen Species J. Immunol., June 15, 2000; 164(12): 6487 - 6494. [Abstract] [Full Text] [PDF]
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M. Lalancette, F. Aoudjit, E. F. Potworowski, and Y. St-Pierre Resistance of ICAM-1-deficient mice to metastasis overcome by increased aggressiveness of lymphoma cells Blood, January 1, 2000; 95(1): 314 - 319. [Abstract] [Full Text] [PDF]
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S. Etienne, S. Bourdoulous, A. D. Strosberg, and P.-O. Couraud MHC Class II Engagement in Brain Endothelial Cells Induces Protein Kinase A-Dependent IL-6 Secretion and Phosphorylation of cAMP Response Element-Binding Protein J. Immunol., October 1, 1999; 163(7): 3636 - 3641. [Abstract] [Full Text] [PDF]
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S. Etienne-Manneville, N. Chaverot, A. D. Strosberg, and P.-O. Couraud ICAM-1-Coupled Signaling Pathways in Astrocytes Converge to Cyclic AMP Response Element-Binding Protein Phosphorylation and TNF-{alpha} Secretion J. Immunol., July 15, 1999; 163(2): 668 - 674. [Abstract] [Full Text] [PDF]
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P. Adamson, S. Etienne, P.-O. Couraud, V. Calder, and J. Greenwood Lymphocyte Migration Through Brain Endothelial Cell Monolayers Involves Signaling Through Endothelial ICAM-1 Via a Rho-Dependent Pathway J. Immunol., March 1, 1999; 162(5): 2964 - 2973. [Abstract] [Full Text] [PDF]
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E. Pluskota, Y. Chen, and S. E. D'Souza Src Homology Domain 2-containing Tyrosine Phosphatase 2 Associates with Intercellular Adhesion Molecule 1 to Regulate Cell Survival J. Biol. Chem., September 22, 2000; 275(39): 30029 - 30036. [Abstract] [Full Text] [PDF]
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