Interplay between integrins and FLK-1 in shear stress-induced signaling.
Interplay between integrins and FLK-1 in shear stress-induced signaling.
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DOI：
10.1152/ajpcell.00222.2002
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发表时间：
2002-11
期刊：
影响因子：
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通讯作者：
Yingxiao Wang;H. Miao;Song Li;Kuang-Den Chen;Yi-Shuan J. Li;Suli Yuan;J. Shyy;S. Chien
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文献类型：
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作者：
Yingxiao Wang;H. Miao;Song Li;Kuang-Den Chen;Yi-Shuan J. Li;Suli Yuan;J. Shyy;S. Chien
血流可以调节血管细胞功能。我们研究了整合素和Flk-1之间的相互作用，在转导的机械剪切应力，由于流动。该阶跃剪切应力的施加引起Flk-1。Casitas B系淋巴瘤（Cbl）活化（Flk-1.在牛主动脉内皮细胞（BAEC）中Cbl结合、Cbl结合的Flk-1的酪氨酸磷酸化和Cbl的酪氨酸磷酸化。通过将BAEC接种在玻连蛋白或纤连蛋白上来激活整合素也诱导了Flk-1。CBL激活。剪切诱导的Flk-1。Cbl的激活被α v β 3或β 1整合素的抑制性抗体阻断，表明它是由整合素介导的。SU 1498对Flk-1的抑制也消除了这种剪切诱导的Flk-1。CBL激活。与Flk-1对整合素的需求相反。Cbl激活，Flk-1阻断剂SU 1498对剪切诱导的整合素激活没有可检测的影响，表明整合素和Flk-1在剪切应力诱导的信号转导层次中起顺序作用。整合素对于通过剪切应力机械活化Flk-1是必需的，但对于通过VEGF化学活化Flk-1不是必需的。
Blood flow can modulate vascular cell functions. We studied interactions between integrins and Flk-1 in transducing the mechanical shear stress due to flow. This application of a step shear stress caused Flk-1. Casitas B-lineage lymphoma (Cbl) activation (Flk-1. Cbl association, tyrosine phosphorylation of the Cbl-bound Flk-1, and tyrosine phosphorylation of Cbl) in bovine aortic endothelial cells (BAECs). The activation of integrins by plating BAECs on vitronectin or fibronectin also induced this Flk-1. Cbl activation. The shear-induced Flk-1. Cbl activation was blocked by inhibitory antibodies for alphavbeta3- or beta1-integrin, suggesting that it is mediated by integrins. Inhibition of Flk-1 by SU1498 also abolished this shear-induced Flk-1. Cbl activation. In contrast to the requirement of integrins for Flk-1. Cbl activation, the Flk-1 blocker SU1498 had no detectable effect on the shear-induced integrin activation, suggesting that integrins and Flk-1 play sequential roles in the signal transduction hierarchy induced by shear stress. Integrins are essential for the mechanical activation of Flk-1 by shear stress but not for the chemical activation of Flk-1 by VEGF.