title: A nuclear tyrosine phosphorylation circuit: c-Jun as an activator and substrate of c-Abl and JNK.
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.
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Barilá
authors.forename: R
authors.initials: R
authors.lastname: Mangano
authors.forename: S
authors.initials: S
authors.lastname: Gonfloni
authors.forename: J
authors.initials: J
authors.lastname: Kretzschmar
authors.forename: M
authors.initials: M
authors.lastname: Moro
authors.forename: D
authors.initials: D
authors.lastname: Bohmann
authors.forename: G
authors.initials: G
authors.lastname: Superti-Furga
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012984:Software; D013379:Substrate Specificity; D014162:Transfection; D014443:Tyrosine; D018909:src Homology Domains
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D014443:Tyrosine; D016315:Proto-Oncogene Proteins c-abl; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases