Differential effects of shear stress and cyclic stretch on focal adhesion remodeling, site-specific FAK phosphorylation, and small GTPases in human lung endothelial cells

Yasushi Shikata, Alexander Rios, Kamon Kawkitinarong, Natacha DePaola, Joe G.N. Garcia, Konstantin G. Birukov

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

Regulation of endothelial cell (EC) permeability by bioactive molecules is associated with specific patterns of cytoskeletal and cell contact remodeling. A role for mechanical factors such as shear stress (SS) and cyclic stretch (CS) in cytoskeletal rearrangements and regulation of EC permeability becomes increasingly recognized. This paper examined redistribution of focal adhesion (FA) proteins, site-specific focal adhesion kinase (FAK) phosphorylation, small GTPase activation and barrier regulation in human pulmonary EC exposed to laminar shear stress (15 dyn/cm2) or cyclic stretch (18% elongation) in vitro. SS caused peripheral accumulation of FAs, whereas CS induced randomly distributed FAs attached to the ends of newly formed stress fibers. SS activated small GTPase Rac without effects on Rho, whereas 18% CS activated without effect on Rac. SS increased transendothelial electrical resistance (TER) in EC monolayers, which was further elevated by barrier-protective phospholipid sphingosine 1-phosphate. Finally, SS induced FAK phosphorylation at Y 576, whereas CS induced FAK phosphorylation at Y397 and Y576. These results demonstrate for the first time differential effects of SS and CS on Rho and Rac activation, FA redistribution, site-specific FAK phosphorylation, and link them with SS-mediated barrier enhancement. Thus, our results suggest common signaling and cytoskeletal mechanisms shared by mechanical and chemical factors involved in EC barrier regulation.

Original languageEnglish (US)
Pages (from-to)40-49
Number of pages10
JournalExperimental Cell Research
Volume304
Issue number1
DOIs
StatePublished - Mar 10 2005
Externally publishedYes

Keywords

  • Cytoskeleton
  • Focal adhesion kinase
  • G-protein-coupled receptor kinase interacting protein
  • Human pulmonary endothelium
  • Paxillin
  • Permeability
  • Rac
  • RhoA

ASJC Scopus subject areas

  • Cell Biology

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