The STAT3 isoforms α and β have unique and specific functions

D Maritano, ML Sugrue, S Tininini, S Dewilde… - Nature …, 2004 - nature.com
D Maritano, ML Sugrue, S Tininini, S Dewilde, B Strobl, XP Fu, V Murray-Tait, R Chiarle
Nature immunology, 2004nature.com
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 STAT3α and the
truncated STAT3β, 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 STAT3β 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 …
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 STAT3α and the truncated STAT3β, 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 STAT3β 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, STAT3α has nonredundant roles such as modulation of cellular responses to IL-6 and mediation of IL-10 function in macrophages.
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