Nuclear translocation of cell adhesion kinase beta/proline-rich tyrosine kinase 2

Cell Struct Funct. 2002 Feb;27(1):47-61. doi: 10.1247/csf.27.47.

Abstract

Cell adhesion kinase beta (CAKbeta/PYK2) is a protein-tyrosine kinase of the focal adhesion kinase (FAK) family. Whereas FAK predominantly localizes at focal adhesions, CAK beta localizes at the perinuclear region in fibroblasts. Here we expressed in cultured cells two point mutants of CAKbeta, P717A and P859A, each of which had lost one of its two PXXP motifs, the ligand sequence for SH3 domains, found at the CAKbeta C-terminal region. We observed a remarkable change in the subcellular distribution of the P859A mutant; while that of the P717A mutant was the same as the wild type. The P859A mutant localized exclusively in the cell nucleus in all cell lines examined. Wild-type CAKbeta also accumulated in the nucleus when cells were treated with an inhibitor of the nuclear export of proteins. These results indicate that CAK beta shuttles between the cytoplasm and the nucleus. On nuclear accumulation of P859A-CAKbeta, a CAKbeta-binding protein, Hic-5, also accumulated in the nucleus. P859A-CAKbeta and co-expressed Hic-5 formed nuclear speckles, in which one other CAK beta-binding protein, p130(Cas), was also concentrated. These findings on nuclear translocation of CAK beta imply that CAKbeta may regulate nuclear processes such as transcription, particularly because Hic-5 was recently shown to be a coactivator of nuclear receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Amino Acid Substitution
  • Animals
  • Binding Sites
  • COS Cells / drug effects
  • COS Cells / metabolism
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Nucleus / enzymology
  • Cell Nucleus / metabolism*
  • Cellular Apoptosis Susceptibility Protein / metabolism*
  • Chlorocebus aethiops
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Dimethyl Sulfoxide / pharmacology
  • Dogs
  • Fatty Acids, Unsaturated / pharmacology
  • Focal Adhesion Kinase 2
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • Osmolar Concentration
  • Paxillin
  • Phosphoproteins / metabolism*
  • Point Mutation
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Rats
  • Subcellular Fractions / enzymology
  • Vanadates / pharmacology

Substances

  • Cellular Apoptosis Susceptibility Protein
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Fatty Acids, Unsaturated
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • PXN protein, human
  • Paxillin
  • Phosphoproteins
  • Pxn protein, rat
  • TGFB1I1 protein, human
  • Tgfb1i1 protein, rat
  • pervanadate
  • Vanadates
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 2
  • Ptk2b protein, rat
  • leptomycin B
  • Dimethyl Sulfoxide