PMID- 10637231 OWN - NLM STAT- MEDLINE DCOM- 20000228 LR - 20181113 IS - 0261-4189 (Print) IS - 0261-4189 (Linking) VI - 19 IP - 2 DP - 2000 Jan 17 TI - A nuclear tyrosine phosphorylation circuit: c-Jun as an activator and substrate of c-Abl and JNK. PG - 273-81 AB - 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. FAU - Barila, D AU - Barila D AD - European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany. FAU - Mangano, R AU - Mangano R FAU - Gonfloni, S AU - Gonfloni S FAU - Kretzschmar, J AU - Kretzschmar J FAU - Moro, M AU - Moro M FAU - Bohmann, D AU - Bohmann D FAU - Superti-Furga, G AU - Superti-Furga G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (Recombinant Proteins) RN - 42HK56048U (Tyrosine) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-abl) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Amino Acid Sequence MH - Animals MH - Cell Line MH - Cell Nucleus/metabolism MH - Enzyme Activation MH - Humans MH - JNK Mitogen-Activated Protein Kinases MH - Mice MH - Mitogen-Activated Protein Kinases/*metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-abl/*metabolism MH - Proto-Oncogene Proteins c-jun/chemistry/*metabolism MH - Recombinant Proteins/chemistry/metabolism MH - Software MH - Substrate Specificity MH - Transfection MH - Tyrosine MH - src Homology Domains PMC - PMC305561 EDAT- 2000/01/19 09:00 MHDA- 2000/03/04 09:00 CRDT- 2000/01/19 09:00 PHST- 2000/01/19 09:00 [pubmed] PHST- 2000/03/04 09:00 [medline] PHST- 2000/01/19 09:00 [entrez] AID - 10.1093/emboj/19.2.273 [doi] PST - ppublish SO - EMBO J. 2000 Jan 17;19(2):273-81. doi: 10.1093/emboj/19.2.273.