首页> 外文期刊>American Journal of Physiology >Focal adhesion kinase modulates activation of NF-kappaB by flow in endothelial cells.
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Focal adhesion kinase modulates activation of NF-kappaB by flow in endothelial cells.

机译:局灶性粘附激酶通过内皮细胞流动调节NF-κB的活化。

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摘要

Atherogenesis involves activation of NF-kappaB in endothelial cells by fluid shear stress. Because this pathway involves integrins, we investigated the involvement of focal adhesion kinase (FAK). We found that FAK was not required for flow-stimulated translocation of the p65 NF-kappaB subunit to the nucleus but was essential for phosphorylation of p65 on serine 536 and induction of ICAM-1, an NF-kappaB-dependent gene. NF-kappaB activation by TNF-alpha or hydrogen peroxide was FAK independent. Events upstream of NF-kappaB, including integrin activation, Rac activation, reactive oxygen production, and degradation of IkappaB, were FAK independent. FAK therefore regulates NF-kappaB phosphorylation and transcriptional activity in response to flow by a novel mechanism.
机译:α闭合涉及通过流体剪切应力激活内皮细胞中的NF-κB。 因为这种途径涉及整联蛋白,所以我们研究了局灶性粘附激酶(FAK)的参与。 我们发现,P65 NF-Kappab亚基对核的流动易刻的FAK不需要FAK,但对于丝氨酸536上p65的磷酸化并且ICAM-1诱导,NF-κB依赖性基因是必要的。 NF-Kappab通过TNF-α或过氧化氢的激活是FAK独立的。 NF-Kappab上游的事件,包括整合素激活,RAC激活,无反应性氧气产量和IKappab的降解,是FAK独立的。 因此,FAK调节NF-Kappab磷酸化和转录活性,以响应于新机制的流动。

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