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Am J Physiol Cell Physiol 283: C1540-C1547, 2002. First published July 24, 2002; doi:10.1152/ajpcell.00222.2002
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Vol. 283, Issue 5, C1540-C1547, November 2002

Interplay between integrins and FLK-1 in shear stress-induced signaling

Yingxiao Wang, Hui Miao, Song Li, Kuang-Den Chen, Yi-Shuan Li, Suli Yuan, John Y.-J. Shyy, and Shu Chien

Department of Bioengineering and Whitaker Institute of Biomedical Engineering, University of California at San Diego, La Jolla, California 92093

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 alpha vbeta 3- or beta 1-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.

mechanotransduction; vascular endothelial growth factor; Casitas B-lineage lymphoma


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