title: Preassociation of nonactivated STAT3 molecules demonstrated in living cells using bioluminescence resonance energy transfer: a new model of STAT activation?
abstract: Signal transducers and activators of transcription (STATs) are crucial molecules in cytokine signaling. In the conventional model of STAT activation, STAT molecules are recruited from a latent pool of cytoplasmic monomers to the activated cytokine receptor. After binding to the receptor, they get tyrosine-phosphorylated, dissociate from the receptor, and translocate to the nucleus as activation-induced dimers. Recently, several publications questioned this model of STAT activation and showed the existence of preassociated STAT molecules before activation. We were able to demonstrate the existence of these preassociated STAT3 molecules in living mammalian cells using bioluminescence resonance energy transfer. Our results support the new hypothesis that STAT molecules exist in the cytoplasm as dimers or multimers and point to an activation-induced change in STAT3 conformation. Therefore, we propose a new model of STAT activation and discuss a hypothetical structure of "cytoplasmic" STAT dimers as opposed to the known "activation-induced" dimer.
authors.affiliation: Institute of Medical Immunology, Humboldt-University (Charite), Berlin, Germany. schrodem@tcd.ie
authors.forename: Martina
authors.initials: M
authors.lastname: Schröder
authors.forename: Karen M
authors.initials: KM
authors.lastname: Kroeger
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Karin A
authors.initials: KA
authors.lastname: Eidne
authors.forename: Gerald
authors.initials: G
authors.lastname: Grütz
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D004735:Energy Transfer; D008156:Luciferases; D008163:Luminescent Measurements; D011485:Protein Binding; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D008156:Luciferases