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Distinct requirements for the naturally occurring splice forms Stat4α and Stat4β in IL‐12 responses
Author(s) -
Hoey Timothy,
Zhang Shangming,
Schmidt Nathan,
Yu Qing,
Ramchandani Shyam,
Xu Xiang,
Naeger Lisa K.,
Sun YaLin,
Kaplan Mark H.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg393
Subject(s) - library science , biology , computer science
Signal transducer and activator of transcription (Stat)4 is a signaling molecule required for normal responses to interleukin‐12 (IL‐12) and is critically involved in inflammatory responses. We have isolated an alternatively spliced isoform of Stat4, termed Stat4β, which lacks 44 amino acids at the C‐terminus, encompassing the putative transcriptional activation domain. To assess the in vivo roles of these Stat4 isoforms, we generated transgenic Stat4‐deficient mice expressing Stat4α or Stat4β. Our results indicate that T‐cell‐specific expression of Stat4α or Stat4β can mediate many aspects of IL‐12 signaling including the differentiation of Th1 cells. However, Stat4α is required for normal levels of IL‐12‐induced interferon‐γ production from Th1 cells. Microarray analysis identified 98 genes induced by both Stat4 isoforms, 32 genes induced only by Stat4α and 29 genes induced only by Stat4β. Some induced genes correlate with specific functions including the ability of Stat4β, but not Stat4α, to mediate IL‐12‐stimulated proliferation. Thus, Stat4α and Stat4β have distinct roles in mediating responses to IL‐12.