A nuclear tyrosine phosphorylation circuit: c-Jun as an activator and substrate of c-Abl and JNK

EMBO J. 2000 Jan 17;19(2):273-81. doi: 10.1093/emboj/19.2.273.


The nuclear function of the c-Abl tyrosine kinase is not well understood. In order to identify nuclear substrates of Abl, we constructed a constitutively active and nuclear form of the protein. We found that active nuclear Abl efficiently phosphorylate c-Jun, a transcription factor not previously known to be tyrosine phosphorylated. After phosphorylation of c-Jun by Abl on Tyr170, both proteins interacted via the SH2 domain of Abl. Surprisingly, elevated levels of c-Jun activated nuclear Abl, resulting in activation of the JNK serine/threonine kinase. This phosphorylation circuit generates nuclear tyrosine phosphorylation and represents a reversal of previously known signalling models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell Nucleus / metabolism
  • Enzyme Activation
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Proto-Oncogene Proteins c-jun / chemistry
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Software
  • Substrate Specificity
  • Transfection
  • Tyrosine
  • src Homology Domains


  • Proto-Oncogene Proteins c-jun
  • Recombinant Proteins
  • Tyrosine
  • Proto-Oncogene Proteins c-abl
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases