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, Shu Chien*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

118 Scopus citations

Abstract

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 αvβ3- or β1-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.

Original languageEnglish
Pages (from-to)C1540-C1547
JournalAmerican Journal of Physiology - Cell Physiology
Volume283
Issue number5 52-5
DOIs
StatePublished - 11 2002
Externally publishedYes

Keywords

  • Casitas B-lineage lymphoma
  • Mechanotransduction
  • Vascular endothelial growth factor

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