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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Acknowledgements
We thank S. Rose John, H. Baumann, U. Müller-Eberhard and W. Liao for the gifts of plasmids; F. Tronche, W. Müller and K. Rajewsky for providing the AlbCre or MxCre transgenic mice; I. Kerr and A. Costa Pereira for ideas and support for the macroarray analysis; S. Pensa and A. Cimino for help with the expression and histological analyses; and I. Kerr, F. Di Cunto, E. Hirsch, F. Bazzoni and T. Alonzi for critically reading the manuscript. Supported by the Wellcome Trust (V.P. and M.L.S.), the Italian Ministry of Research (MIUR) and the Italian Cancer Research Association (AIRC). D.M. was the recipient of a Marie Curie European Community post-doctoral fellowship.
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Maritano, D., Sugrue, M., Tininini, S. et al. The STAT3 isoforms α and β have unique and specific functions. Nat Immunol 5, 401–409 (2004). https://doi.org/10.1038/ni1052
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DOI: https://doi.org/10.1038/ni1052
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