VEGF induces nuclear translocation of Flk-1/KDR, endothelial nitric oxide synthase, and caveolin-1 in vascular endothelial cells

Biochem Biophys Res Commun. 1999 Mar 5;256(1):192-7. doi: 10.1006/bbrc.1998.9790.

Abstract

VEGF increases endothelial cell permeability and growth by a process requiring NOS activity. Because eNOS activity is regulated by its interaction with the caveolar structural protein caveolin-1, we analyzed VEGF effects on structural interactions between eNOS, caveolin-1 and the VEGF receptor Flk-1/KDR. Confocal immunolocalization analysis of the subcellular distribution of Flk-1/KDR, caveolin-1 and eNOS showed that VEGF stimulated the translocation of all three proteins into the nucleus. This result was confirmed by cell fractionation and immunoblotting studies showing that levels of all three proteins within the caveolar compartment declined progressively after 30 and 60 min of VEGF treatment. The pattern was reversed for nuclear fractions. Protein levels were lowest in the control cultures, but increased progressively after 30 and 60 min of treatment. Nuclear translocation of eNOS and Flk-1/KDR within caveolae may represent a mechanism for targeting NO production to the nuclear compartment where it could influence transcription factor activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta
  • Blotting, Western
  • Cattle
  • Caveolin 1
  • Caveolins*
  • Cell Fractionation
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism*
  • Cells, Cultured
  • Endothelial Growth Factors / pharmacology*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Immunohistochemistry
  • Lymphokines / pharmacology*
  • Membrane Proteins / metabolism*
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type III
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Growth Factor / metabolism*
  • Receptors, Vascular Endothelial Growth Factor
  • Retina
  • Signal Transduction / drug effects
  • Time Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Caveolin 1
  • Caveolins
  • Endothelial Growth Factors
  • Lymphokines
  • Membrane Proteins
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor