Angiotensin converting enzyme (ACE) and ACE2 bind integrins and ACE2 regulates integrin signalling.
Angiotensin converting enzyme (ACE) and ACE2 bind integrins and ACE2 regulates integrin signalling.
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DOI：
10.1371/journal.pone.0034747
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Turner AJ
中科院分区：
文献类型：
--
作者：
Clarke NE;Fisher MJ;Porter KE;Lambert DW;Turner AJ
血管紧张素转换酶（ace）是肾素-血管紧张素系统的关键催化成分，通过平衡彼此的作用来调节血压的精确调节。抑制ACE已被证明可以改善心血管疾病的病理，而ACE2在衰竭的心脏中具有心脏保护作用。然而，ACE2介导其心脏保护功能的机制尚未完全阐明。在这里，我们证明了ACE和ACE2都以不依赖于rgd的方式结合整合素亚基，并且它们可以作为细胞粘附底物。我们发现ACE2的表达增强了细胞粘附。此外，我们提出证据表明可溶性ACE2 （sACE2）能够抑制FAK介导的整合素信号传导。此外，sACE2增加Akt的表达，从而降低信号分子磷酸化Akt的比例。这些结果表明，ACE2在细胞-细胞相互作用中发挥作用，可能对整合素信号传导进行微调。因此，ACE2在质膜上的表达和裂解可能影响细胞与细胞外基质的相互作用以及介导细胞存活和增殖的信号传导。因此，ACE2的外畴脱落可能在病理性心脏重构过程中发挥作用。
The angiotensin converting enzymes (ACEs) are the key catalytic components of the renin-angiotensin system, mediating precise regulation of blood pressure by counterbalancing the effects of each other. Inhibition of ACE has been shown to improve pathology in cardiovascular disease, whilst ACE2 is cardioprotective in the failing heart. However, the mechanisms by which ACE2 mediates its cardioprotective functions have yet to be fully elucidated. Here we demonstrate that both ACE and ACE2 bind integrin subunits, in an RGD-independent manner, and that they can act as cell adhesion substrates. We show that cellular expression of ACE2 enhanced cell adhesion. Furthermore, we present evidence that soluble ACE2 (sACE2) is capable of suppressing integrin signalling mediated by FAK. In addition, sACE2 increases the expression of Akt, thereby lowering the proportion of the signalling molecule phosphorylated Akt. These results suggest that ACE2 plays a role in cell-cell interactions, possibly acting to fine-tune integrin signalling. Hence the expression and cleavage of ACE2 at the plasma membrane may influence cell-extracellular matrix interactions and the signalling that mediates cell survival and proliferation. As such, ectodomain shedding of ACE2 may play a role in the process of pathological cardiac remodelling.
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DOI：
10.4049/jimmunol.1100646
发表时间：
2011-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Long EO
通讯作者：
Long EO
影响因子：
7.8
作者：
BARSHAVIT, R;ESKOHJIDO, Y;VLODAVSKY, I
通讯作者：
VLODAVSKY, I
影响因子：
--
作者：
Ji, Yuanyuan;Liu, Juntian;Liu, Na
通讯作者：
Liu, Na
DOI：
10.1016/j.bbadis.2004.05.005
发表时间：
2004-08-04
影响因子：
6.2
作者：
Lin, QS;Keller, RS;Zisman, LS
通讯作者：
Zisman, LS
心肌梗塞会增加大鼠和人类 ACE2 的表达
影响因子：
39.3
作者：
Burrell, LM;Risvanis, J;Johnston, CI
通讯作者：
Johnston, CI