Nuclear localization and apoptotic regulation of an amino-terminal domain focal adhesion kinase fragment in endothelial cells

Biochem Biophys Res Commun. 2000 Oct 5;276(3):1068-74. doi: 10.1006/bbrc.2000.3547.


This study investigated the subcellular compartmentalization of focal adhesion kinase (FAK) fragments and their regulation during apoptosis of human umbilical vein endothelial cells. A 50 kDa NH(2)-terminal FAK fragment and a 120 kDa FAK variant were constitutively expressed and specifically found in the nuclear fraction of cells, while a 55 kDa COOH-terminal FAK fragment was only in the cytosolic fraction. FAK cleavage fragments generated during apoptosisremained in the cytosol, while p120FAK and p50 NH(2)-terminal FAK remained in the nuclear compartment. The caspase inhibitor, ZVAD-fmk, prevented the apoptosis-induced proteolysis of p125 and p120FAK, generation of the 80 kDa cleavage product, and increased expression of p50N-FAK. Western blot with phospho-specific FAK showed that nuclear p125(FAK) was phosphorylated at a significant level at Y861, while FAK phosphorylated at Y397 and Y407 was largely in the cytosol. These results indicate that FAK NH(2)- and COOH-terminal domain fragments are segregated between nuclear and cytosolic compartments in endothelial cells and suggest novel functions for the FAK NH(2)-terminal domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Apoptosis*
  • Blotting, Western
  • Caspase Inhibitors
  • Caspases / metabolism
  • Cell Nucleus / drug effects
  • Cell Nucleus / enzymology
  • Cell Nucleus / metabolism*
  • Cells, Cultured
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / metabolism*
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Humans
  • In Situ Nick-End Labeling
  • Molecular Weight
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Phosphorylation / drug effects
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / chemistry*
  • Protein-Tyrosine Kinases / metabolism*
  • Staurosporine / antagonists & inhibitors
  • Staurosporine / pharmacology


  • Caspase Inhibitors
  • Peptide Fragments
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human
  • Caspases
  • Staurosporine