title: A STAT3 dimer formed by inter-chain disulphide bridging during oxidative stress.
abstract: Signal transducer and activator of transcription (STAT) proteins are activated by cytokines and growth factors to play distinct roles in immune responses and developmental processes. STATs were thought to exist as latent, cytoplasmic monomers and activation to require dimer formation was mediated exclusively by reciprocal phospho-tyrosine/SH2-domain interactions, but recent evidence of cytoplasmic STAT complexes, including dimers, and unphosphorylated STATs in the nucleus has challenged these notions. STAT complexes detected by conventional SDS-PAGE, including a STAT3 dimer, have been reported. We show that such complexes can form during cell lysis and be disrupted with DTT, suggesting inter-chain disulphide bridging. STAT3 also forms a related complex in cells upon oxidative stress. We map the interaction to the amino-terminal domain of STAT3 and use mass spectrometry to implicate cysteine 259 as the reactive residue. The redox sensitivity of STAT3 may be significant, given its activation in cells in response to reactive oxygen species.
authors.affiliation: School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Peter E
authors.initials: PE
authors.lastname: Shaw
mesh_terms: D000209:Acute-Phase Proteins / Q000737:chemistry / Q000378:metabolism; D001402:B-Lymphocytes; D001943:Breast Neoplasms; D002460:Cell Line; D045744:Cell Line, Tumor; D003545:Cysteine / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry*; D006801:Humans; D007668:Kidney; D018384:Oxidative Stress / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D000209:Acute-Phase Proteins; D004268:DNA-Binding Proteins; D004220:Disulfides; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D003545:Cysteine