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

D Barilá1, R Mangano, S Gonfloni

  • 1European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.

The EMBO Journal
|January 19, 2000
PubMed

Insights

Nuclear Abl kinase phosphorylates c-Jun, a transcription factor, revealing a new signaling pathway. This interaction activates JNK, reversing known models and highlighting nuclear tyrosine phosphorylation.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • The nuclear role of c-Abl tyrosine kinase remains largely uncharacterized.
  • Identifying nuclear substrates is crucial for understanding Abl's function in the nucleus.

Purpose of the Study:

  • To identify nuclear substrates of the c-Abl tyrosine kinase.
  • To investigate the functional consequences of nuclear Abl activity.

Main Methods:

  • Constructed a constitutively active, nuclear form of c-Abl.
  • Utilized biochemical assays to detect protein phosphorylation and interaction.

Main Results:

  • Discovered that active nuclear Abl efficiently phosphorylates c-Jun on Tyr170.
  • Demonstrated a novel interaction between phosphorylated c-Jun and Abl via the Abl SH2 domain.
  • Observed that elevated c-Jun levels activate nuclear Abl, subsequently activating JNK kinase.

Conclusions:

  • c-Jun is a novel nuclear substrate for c-Abl tyrosine kinase.
  • A positive feedback loop exists where c-Jun activates nuclear Abl, leading to JNK activation.
  • This pathway represents a reversal of established signaling models, introducing nuclear tyrosine phosphorylation.

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