The STAT3 isoforms alpha and beta have unique and specific functions.
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.
Maritano
Diego
D
Department of Genetics, Biology and Biochemistry, University of Turin, 10126 Turin, Italy.
Sugrue
Michelle L
ML
Tininini
Silvia
S
Dewilde
Sarah
S
Strobl
Birgit
B
Fu
XinPing
X
Murray-Tait
Victoria
V
Chiarle
Roberto
R
Poli
Valeria
V
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*
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D020033:Protein Isoforms; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators