Integrin signaling in vascular function.
Integrin signaling in vascular function.
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DOI：
10.1097/moh.0b013e3283523df0
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发表时间：
2012-05
影响因子：
3.2
通讯作者：
Byzova TV
中科院分区：
文献类型：
--
作者：
Malinin NL;Pluskota E;Byzova TV
本文综述了整合素及其相关蛋白在血管特异性功能和调控方面的最新进展，包括我们对整合素由内而外激活的理解。2009年，随着Kindlin蛋白家族成员被鉴定为整合素由内而外信号传导的重要介质，对整合素活化调控的研究受到了新的推动。在当前的综述中，我们概述了Kindlins在血管系统中作用的最新发现，以及已经开始塑造Kindlins功能机制模型的新研究。近年来，整合素及其功能相关基因的组织特异性敲除模型已被提出，包括平滑肌特异性ILK、内皮特异性FAK和Talin-1的敲除。在杂合子动物敲除模型中，Kindlin-2已被证明是血管生成和血管通透性的重要调节剂。由于大量的论文已经推进了我们对Kindlin函数的理解，因此对它们进行了更详细的回顾和讨论。新发现包括Kindlin分子内的额外脂质结合位点和β-整联蛋白的非磷酸化形式的优先结合。整合素在血管生成中的作用已被证明包括，除了细胞粘附和机械转导，特定的信号传导功能。整合素由内而外途径在血管生理学中的重要性已被明确证实，内皮通透性直接受此过程调节。抑制由内而外途径中的Kindlin依赖性步骤作为阻断血小板聚集的方法应该是旁系同源特异性的，因为它可能对血管通透性产生不利影响。
In the current review, we summarize recent progress on vasculature-specific function and regulation of integrins and integrin-associated proteins, including advances in our understanding of inside-out integrin activation. The studies on regulation of integrin activation received new impulse in 2009 with the identification of Kindlin protein family members as crucial mediators of integrin inside-out signaling. In the current review, we outline the recent findings on the role of Kindlins in the vascular system, as well as new studies that have begun shaping the mechanistic model of Kindlins’ function. Several tissue-specific knockout models for integrins and genes associated with the integrin functions have been recently presented, including smooth muscle-specific ILK and endothelial-specific FAK and Talin-1 ablation. In the heterozygous animal knockout model, Kindlin-2 has been demonstrated as a crucial modulator of angiogenesis and vascular permeability. As a number of papers have advanced our understanding of Kindlin function, they are reviewed and discussed in further detail. New findings include an additional lipid binding site within the Kindlin molecule and preferential binding of non-phosphorylated form of β-integrins. The role of integrins in angiogenesis has been demonstrated to include, in addition to cell adhesion and mechanotransduction, specific signaling functions. The importance of integrin inside-out pathway in vascular physiology has been unequivocally proven, and endothelial permeability is directly regulated by this process. Inhibition of Kindlin-dependent steps in the inside-out pathway as an approach to block platelet aggregation should be paralog-specific, as it may have adverse effects on vascular permeability.