KLF2-induced actin shear fibers control both alignment to flow and JNK signaling in vascular endothelium

Blood. 2010 Mar 25;115(12):2533-42. doi: 10.1182/blood-2009-06-228726. Epub 2009 Dec 23.


The shear stress-induced transcription factor Krüppel-like factor 2 (KLF2) confers antiinflammatory properties to endothelial cells through the inhibition of activator protein 1, presumably by interfering with mitogen-activated protein kinase (MAPK) cascades. To gain insight into the regulation of these cascades by KLF2, we used antibody arrays in combination with time-course mRNA microarray analysis. No gross changes in MAPKs were detected; rather, phosphorylation of actin cytoskeleton-associated proteins, including focal adhesion kinase, was markedly repressed by KLF2. Furthermore, we demonstrate that KLF2-mediated inhibition of Jun NH(2)-terminal kinase (JNK) and its downstream targets ATF2/c-Jun is dependent on the cytoskeleton. Specifically, KLF2 directs the formation of typical short basal actin filaments, termed shear fibers by us, which are distinct from thrombin- or tumor necrosis factor-alpha-induced stress fibers. KLF2 is shown to be essential for shear stress-induced cell alignment, concomitant shear fiber assembly, and inhibition of JNK signaling. These findings link the specific effects of shear-induced KLF2 on endothelial morphology to the suppression of JNK MAPK signaling in vascular homeostasis via novel actin shear fibers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Activating Transcription Factor 2 / metabolism
  • Animals
  • Aorta / cytology
  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism*
  • Femoral Artery / cytology
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • MAP Kinase Signaling System / physiology*
  • Phosphorylation / physiology
  • Rats
  • Regional Blood Flow / physiology
  • Saphenous Vein / cytology
  • Stress, Mechanical
  • Transduction, Genetic
  • Umbilical Veins / cytology
  • rho-Associated Kinases / metabolism


  • ATF2 protein, human
  • Activating Transcription Factor 2
  • KLF2 protein, human
  • Kruppel-Like Transcription Factors
  • rho-Associated Kinases
  • JNK Mitogen-Activated Protein Kinases