The focal adhesion kinase amino-terminal domain localises to nuclei and intercellular junctions in HEK 293 and MDCK cells independently of tyrosine 397 and the carboxy-terminal domain

Biochem Biophys Res Commun. 2002 Nov 22;299(1):62-73. doi: 10.1016/s0006-291x(02)02547-0.


The function and intracellular localisation of the non-catalytic NH(2)-terminal region of focal adhesion kinase (FAK) are unclear. We investigated the targetting of the FAK NH(2)-terminal domain in HEK 293 and epithelial MDCK cells. Exogenous expression of a variety of GFP-fused and epitope-tagged NH(2) terminal domain constructs either including or lacking the major Tyr 397 autophosphorylation and Src-binding site targeted to nuclei and cell-cell junctions in HEK 293 cells and co-localised at junctions with occludin, and beta1 integrin subunits at junctions. Mutation of Tyr 397 also had no effect on localisation of the NH(2)-terminal domain. In contrast, constructs encoding either the kinase or focal adhesion targeting (FAT) domains but lacking the NH(2)-terminal region failed to localise to intercellular junctions or nuclei. The NH(2)-terminal domain was not associated with beta1 integrin subunits as indicated by co-immunoprecipitation experiments, but did co-localise with cortical actin filaments. The NH(2)-terminal domain also targetted to nuclei and intercellular junctions in MDCK cells, whereas full-length FAK localised only to focal adhesions in these cells. These results indicate that the FAK NH(2)-terminal domain targets to epithelial intercellular junctions and nuclei and suggest novel functions for FAK NH(2)-terminal domain fragments independent of Y397, kinase, and FAT domains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Binding Sites
  • Cell Line
  • Cell Nucleus / metabolism*
  • Cells, Cultured
  • DNA, Complementary / metabolism
  • Dogs
  • Epithelial Cells / metabolism
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Green Fluorescent Proteins
  • Humans
  • Immunohistochemistry
  • Integrin beta1 / metabolism
  • Intercellular Junctions / metabolism*
  • Luminescent Proteins / metabolism
  • Microscopy, Confocal
  • Mutation
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / chemistry*
  • Transfection
  • Tyrosine / chemistry


  • Actins
  • DNA, Complementary
  • Integrin beta1
  • Luminescent Proteins
  • Green Fluorescent Proteins
  • Tyrosine
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human