title: The STAT3 isoforms alpha and beta have unique and specific functions.
abstract: Signal transducer and activator of transcription 3 (STAT3) is the main mediator of interleukin 6 (IL-6)-type cytokine signaling. It exists in two isoforms: the full-length STAT3 alpha and the truncated STAT3 beta, generally thought to act as a dominant negative factor. To assess their relative functions, we ablated the expression of either isoform by gene targeting. We show here that in vivo STAT3 beta is not a dominant negative factor. Its expression can rescue the embryonic lethality of a STAT3-null mutation and it can by itself induce the expression of specific STAT3 target genes. Nevertheless, STAT3 alpha has nonredundant roles such as modulation of cellular responses to IL-6 and mediation of IL-10 function in macrophages.
authors.affiliation: Department of Genetics, Biology and Biochemistry, University of Turin, 10126 Turin, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Maritano
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Sugrue
authors.forename: Silvia
authors.initials: S
authors.lastname: Tininini
authors.forename: Sarah
authors.initials: S
authors.lastname: Dewilde
authors.forename: Birgit
authors.initials: B
authors.lastname: Strobl
authors.forename: XinPing
authors.initials: X
authors.lastname: Fu
authors.forename: Victoria
authors.initials: V
authors.lastname: Murray-Tait
authors.forename: Roberto
authors.initials: R
authors.lastname: Chiarle
authors.forename: Valeria
authors.initials: V
authors.lastname: Poli
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005298:Fertility / Q000235:genetics*; D005804:Genes, Lethal; D015151:Immunoblotting; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D015850:Interleukin-6; D020033:Protein Isoforms; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators