Article
- The EMBO Journal (2000) 19, 273 - 281
- doi:10.1093/emboj/19.2.273
A nuclear tyrosine phosphorylation circuit: c-Jun as an activator and substrate of c-Abl and JNK
Daniela Barilá1, Raffaella Mangano1, Stefania Gonfloni1, Jana Kretzschmar1, Marina Moro2, Dirk Bohmann1 and Giulio Superti-Furga1
- European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
- Present address: Pharmacia & Upjohn Diagnostics AB, S-751 82 Uppsala, Sweden
Correspondence to:
Giulio Superti-Furga, E-mail: superti@embl-heidelberg.de
Received 2 August 1999; Accepted 11 November 1999; Revised 10 November 1999
Abstract
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.
Keywords:
- Abl,
- JNK,
- Jun,
- nuclear tyrosine phosphorylation,
- phosphorylation circuit
