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PECAM-1 engagement counteracts ICAM-1-induced signaling in brain vascular endothelial cells.

Authors: Couty, JP  Rampon, C  Leveque, M  Laran-Chich, MP  Bourdoulous, S  Greenwood, J  Couraud, PO 
Citation: Couty JP, etal., J Neurochem. 2007 Oct;103(2):793-801. Epub 2007 Jul 27.
Pubmed: (View Article at PubMed) PMID:17662049
DOI: Full-text: DOI:10.1111/j.1471-4159.2007.04782.x

Interactions between leukocytes and vascular endothelial cells are mediated by a complex set of membrane adhesion molecules which transduce bi-directional signals in both cell types. Endothelium of the cerebral blood vessels, which constitute the blood-brain barrier, strictly controls adhesion and trafficking of leukocytes into the brain. Investigating signaling pathways triggered by the engagement of adhesion molecules expressed on brain endothelial cells, we previously documented the role of ICAM-1 in activation of the tyrosine phosphorylation of several actin-binding proteins and subsequent rearrangements of the actin cytoskeleton. In the present study, we show that, whereas PECAM-1 is known to control positively the trans-endothelial migration of leukocytes via homophilic interactions between leukocytes and endothelial cells, PECAM-1 engagement on brain endothelial surface unexpectedly counteracts the ICAM-1-induced tyrosine phosphorylation of cortactin and rearrangements of the actin cytoskeleton. We present evidence that the PECAM-1-associated tyrosine phosphatase SHP-2 is required for ICAM-1 signaling, suggesting that its activity might crucially contribute to the regulation of ICAM-1 signaling by PECAM-1. Our findings reveal a novel activity for PECAM-1 which, by counteracting ICAM-1-induced activation, could directly contribute to limit activation and maintain integrity of brain vascular endothelium.


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CRRD Object Information
CRRD ID: 7240703
Created: 2013-02-19
Species: All species
Last Modified: 2013-02-19
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.