The STAT3 isoforms α and β have unique and specific functions

• Published in: Nature immunology Vol. 5; no. 4; pp. 401 - 409
• Main Authors: Poli, Valeria, Maritano, Diego, Sugrue, Michelle L, Tininini, Silvia, Dewilde, Sarah, Strobl, Birgit, Fu, XinPing, Murray-Tait, Victoria, Chiarle, Roberto
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.04.2004
• Subjects: Animals; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fertility - genetics; Genes, Lethal; Immunoblotting; Inflammation - metabolism; Interleukin-6 - metabolism; Kidney - pathology; Liver - immunology; Liver - metabolism; Liver - pathology; Lung - pathology; Mice; Mutation; Protein Isoforms - genetics; Protein Isoforms - metabolism; STAT3 Transcription Factor; Trans-Activators - deficiency; Trans-Activators - genetics; Trans-Activators - metabolism
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni1052

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.