首页> 外文期刊>Journal of vascular research >Characterization and regulation of the receptor tyrosine kinase Tie-1 in platelets.
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Characterization and regulation of the receptor tyrosine kinase Tie-1 in platelets.

机译:血小板中受体酪氨酸激酶Tie-1的表征和调控。

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The receptor tyrosine kinase Tie-1 is expressed predominantly on endothelial cells where it has an essential role in blood vessel formation. Targeted disruption of the Tie-1 gene results in a lethal phenotype with severe disruption to the normal integrity of the vasculature. In an examination of Tie-1 in vivo, we observed a significant pool of the receptor present in the circulation associated with the platelet fraction. Western blotting reveals the platelet form of Tie-1 to be a protein of approximately 110 kDa, this contrasts with the 135/125-kDa doublet found in endothelial cells. Platelet activation results in increased surface expression of Tie-1. The closely related receptor tyrosine kinase Tie-2/Tek is not present in platelets. Endothelial Tie-1 undergoes metalloprotease-mediated ectodomain cleavage in response to phorbol ester and other agonists. Tie-1 cleavage leads to release of the extracellular domain and generation of a cell-associated intracellular domain with signalling capacity. The potential for cleavage was investigated in platelets. In contrast to endothelial Tie-1, phorbol ester does not stimulate truncation of the platelet receptor, suggesting these cells lack one or more components of the regulated metalloprotease system controlling Tie-1. These data demonstrate the Tie-1 receptor tyrosine kinase is present on platelets and its surface expression is regulated. Furthermore, platelet Tie-1 differs significantly from the endothelial receptor. Platelet Tie-1 has the potential to modulate endothelial function by competing for any Tie ligands and may have signalling roles important in controlling aspects of platelet behaviour. Copyright 2000 S. Karger AG, Basel
机译:受体酪氨酸激酶Tie-1主要在内皮细胞上表达,在内皮细胞中它在血管形成中起重要作用。 Tie-1基因的靶向破坏会导致致命的表型,严重破坏脉管系统的正常完整性。在体内Tie-1的检查中,我们观察到与血小板部分相关的循环中存在大量的受体。蛋白质印迹显示血小板形式的Tie-1是大约110 kDa的蛋白质,这与内皮细胞中的135 / 125-kDa双峰形成了对比。血小板活化导致Tie-1的表面表达增加。血小板中不存在紧密相关的受体酪氨酸激酶Tie-2 / Tek。响应于佛波酯和其他激动剂,内皮Tie-1经历了金属蛋白酶介导的胞外域裂解。 Tie-1切割导致释放胞外域,并产生具有信号传导能力的细胞相关胞内域。在血小板中研究了切割的可能性。与内皮Tie-1相比,佛波酯不刺激血小板受体的截短,表明这些细胞缺乏控制Tie-1的金属蛋白酶体系的一种或多种成分。这些数据证明Tie-1受体酪氨酸激酶存在于血小板上,并且其表面表达受到调节。此外,血小板Tie-1与内皮受体明显不同。血小板Tie-1具有通过竞争任何Tie配体来调节内皮功能的潜力,并且可能在控制血小板行为方面具有重要的信号传导作用。版权所有2000 S. Karger AG,巴塞尔

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