Nuclear localization and possible functions of receptor tyrosine kinases

Curr Opin Cell Biol. 2003 Apr;15(2):143-8. doi: 10.1016/s0955-0674(03)00015-2.


Recent data have renewed interest in the possible nuclear localization of receptor tyrosine kinases, as well as their ligands. In one case, that of ErbB-4, the receptor is processed by two membrane-localized proteases to produce a soluble cytoplasmic domain fragment that includes the tyrosine kinase domain. This fragment, generated by a metalloprotease-dependent ectodomain cleavage followed by gamma-secretase cleavage within the transmembrane domain, is also found in the nucleus. Three other receptor tyrosine kinases have been detected in the nucleus in the absence of proteolytic processing. In some instances, nuclear localization of receptor tyrosine kinases is growth-factor-dependent and tentative evidence suggests a role in transcription.

Publication types

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

MeSH terms

  • Animals
  • Cell Nucleus / metabolism*
  • ErbB Receptors / metabolism*
  • Eukaryotic Cells / metabolism*
  • Eukaryotic Cells / ultrastructure
  • Growth Substances / metabolism
  • Humans
  • Peptide Fragments / metabolism
  • Protein Structure, Tertiary / physiology
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, ErbB-4
  • Transcription Factors / physiology*


  • Growth Substances
  • Peptide Fragments
  • Transcription Factors
  • ERBB4 protein, human
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-4