Mechanotransduction in Endothelial Cells: Temporal Signaling Events in Response to Shear StressTakahashi M. · Ishida T. · Traub O. · Corson M.A. · Berk B.C.
Division of Cardiology, Department of Medicine, University of Washington School of Medicine, Seattle, Wash., USA
Fluid shear stress is one of the most important mechanical forces acting upon vascular endothelium, because of its location at the interface between the bloodstream and vascular wall. Recent evidence indicates that several intracellular signaling events are stimulated in endothelial cells in response to shear stress. Through these events, shear stress modulates endothelial cell function and vascular structure, but the molecular basis of shear stress mechanotransduction remains to be elucidated. In our research we have focused on three temporal signal responses to shear stress: (1) production of nitric oxide (NO) as an immediate response; (2) activation of extracellular-regulated kinases (ERK1/2; p44/p42 mitogen-activated protein (MAP) kinases) as a rapid response, and (3) tyrosine phosphorylation of focal adhesion kinase (FAK) as a sustained response. In terms of vessel biology, NO production, and ERK1/2 and FAK activation seem to be correlated with vascular homeostasis, gene expression and cytoskeletal rearrangement, respectively. In this review, we discuss the mechanisms that establish the temporal order of shear stress-stimulated responses based on a hierarchy for assembly of signal transduction molecules at the cell plasma membrane.
© 1997 S. Karger AG, Basel
Bradford C. Berk, MD, PhD, University of Washington, Division of Cardiology, Box 357710, Seattle, WA 98195 (USA), Tel. (206) 685-6960, Fax (206) 616-5156, E-Mail: firstname.lastname@example.org
Received: October 23, 1996
Accepted after revision: December 18, 1996
Published online: September 24, 2008
Number of Print Pages : 8
Journal of Vascular Research (Incorporating 'International Journal of Microcirculation')
Vol. 34, No. 3, Year 1997 (Cover Date: 1997)
Journal Editor: Pohl U. (Munich), Meininger G.A. (Columbia, Mo.)
ISSN: 1018–1172 (Print), eISSN: 1423–0135 (Online)
For additional information: http://www.karger.com/JVR