PECAM-1 engagement counteracts ICAM-1-induced signaling in brain vascular endothelial cells.
PECAM-1 engagement counteracts ICAM-1-induced signaling in brain vascular endothelial cells.
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DOI：
10.1111/j.1471-4159.2007.04782.x
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发表时间：
2007-10
影响因子：
4.7
通讯作者：
Couraud PO
中科院分区：
文献类型：
--
作者：
Couty JP;Rampon C;Leveque M;Laran-Chich MP;Bourdoulous S;Greenwood J;Couraud PO
白细胞和血管内皮细胞之间的相互作用是由一组复杂的膜粘附分子介导的，这些分子在两种细胞类型中传递双向信号。构成血脑屏障的脑血管内皮严格控制白细胞进入大脑的粘附和运输。为了研究脑内皮细胞上表达的粘附分子参与引发的信号通路，我们之前记录了ICAM-1在激活几种肌动蛋白结合蛋白的酪氨酸磷酸化和随后的肌动蛋白细胞骨架重排中的作用。在目前的研究中，我们发现，尽管已知PECAM-1通过白细胞与内皮细胞之间的亲同性相互作用积极控制白细胞的跨内皮迁移，但PECAM-1在脑内皮表面的作用出人意料地抵消了icam -1诱导的酪氨酸磷酸化的皮质蛋白和肌动蛋白细胞骨架的重排。我们提供的证据表明，与PECAM-1相关的酪氨酸磷酸酶SHP-2是ICAM-1信号转导所必需的，这表明其活性可能对PECAM-1对ICAM-1信号转导的调节至关重要。我们的研究结果揭示了PECAM-1的一种新活性，它可以通过抵消icam -1诱导的激活，直接有助于限制激活和维持脑血管内皮的完整性。
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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VCAM-1和ICAM-1与粘附白细胞的新型内皮对接结构中的动态相互作用。
DOI：
10.1083/jcb.200112126
发表时间：
2002-06-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Barreiro O;Yanez-Mo M;Serrador JM;Montoya MC;Vicente-Manzanares M;Tejedor R;Furthmayr H;Sanchez-Madrid F
通讯作者：
Sanchez-Madrid F
DOI：
10.1083/jcb.200106148
发表时间：
2001-10-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hoffmann I;Eugène E;Nassif X;Couraud PO;Bourdoulous S
通讯作者：
Bourdoulous S
影响因子：
4.4
作者：
Carman, CV;Jun, CD;Springer, TA
通讯作者：
Springer, TA
影响因子：
4
作者：
Greenwood, J;Etienne-Manneville, S;Couraud, PO
通讯作者：
Couraud, PO
影响因子：
5.5
作者：
Gopalakrishnan, S;Hallett, MA;Marrs, JA
通讯作者：
Marrs, JA