Identification of a signal for rapid export of proteins from the nucleus

Cell. 1995 Aug 11;82(3):463-73. doi: 10.1016/0092-8674(95)90435-2.


Active nuclear import of protein is controlled by nuclear localization signals (NLSs), but nuclear export is not understood well. Nuclear trafficking of the catalytic (C) subunit of cAMP-dependent protein kinase (cAPK) is critical for regulation of gene expression. The heat-stable inhibitor (PKl) of cAPK contains a nuclear export signal (NES) that triggers rapid, active net extrusion of the C-PKl complex from the nucleus. This NES (residues 35-49), fused or conjugated to heterologous proteins, was sufficient for rapid nuclear export. Hydrophobic residues were critical. The NES is a slightly weaker signal than the SV40 NLS. A sequence containing only residues 37-46, LALKLAGLDI, is also sufficient for nuclear export. This is an example of a protein-based NES having no obvious association with RNA. A similar sequence, LQLPPLERLTL, from Rev, an RNA-binding protein of HIV-1, also is an NES.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Transport
  • Cell Line
  • Cell Nucleus / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression Regulation
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Kinase Inhibitors*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism


  • Protein Kinase Inhibitors
  • Recombinant Fusion Proteins
  • Cyclic AMP-Dependent Protein Kinases