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.

The STAT3 isoforms alpha and beta have unique and specific functions

MARITANO, DIEGO;DEWILDE, SARAH;CHIARLE, Roberto;POLI, Valeria
2004-01-01

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.
2004
5
401
409
http://www.nature.com/ni/journal/v5/n4/pdf/ni1052.pdf
Stat3; Stat3 isoforms; isoform ablation; IL-6 signalling; gene targeting; knock-in; inflammation.
MARITANO D; SUGRUE ML; TINININI S; DEWILDE S; STROBL B; FU X; MURRAY-TAIT V; CHIARLE R; POLI V.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/37262
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