Distinct requirements for the naturally occurring splice forms Stat4α and Stat4β in IL-12 responses

Timothy Hoey, Shangming Zhang, Nathan Schmidt, Qing Yu, Shyam Ramchandani, Xiang Xu, Lisa K. Naeger, Ya Lin Sun, Mark Kaplan

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4237-4248
Number of pages12
JournalEMBO Journal
Volume22
Issue number16
DOIs
StatePublished - Aug 15 2003

Fingerprint

Interleukin-12
Genes
Protein Isoforms
Th1 Cells
STAT4 Transcription Factor
T-cells
Microarray Analysis
Microarrays
Interferons
Transcriptional Activation
Chemical activation
T-Lymphocytes
Amino Acids
Molecules

Keywords

  • IL-12
  • Stat4
  • T-helper cells
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Distinct requirements for the naturally occurring splice forms Stat4α and Stat4β in IL-12 responses. / Hoey, Timothy; Zhang, Shangming; Schmidt, Nathan; Yu, Qing; Ramchandani, Shyam; Xu, Xiang; Naeger, Lisa K.; Sun, Ya Lin; Kaplan, Mark.

In: EMBO Journal, Vol. 22, No. 16, 15.08.2003, p. 4237-4248.

Research output: Contribution to journalArticle

Hoey, T, Zhang, S, Schmidt, N, Yu, Q, Ramchandani, S, Xu, X, Naeger, LK, Sun, YL & Kaplan, M 2003, 'Distinct requirements for the naturally occurring splice forms Stat4α and Stat4β in IL-12 responses', EMBO Journal, vol. 22, no. 16, pp. 4237-4248. https://doi.org/10.1093/emboj/cdg393
Hoey, Timothy ; Zhang, Shangming ; Schmidt, Nathan ; Yu, Qing ; Ramchandani, Shyam ; Xu, Xiang ; Naeger, Lisa K. ; Sun, Ya Lin ; Kaplan, Mark. / Distinct requirements for the naturally occurring splice forms Stat4α and Stat4β in IL-12 responses. In: EMBO Journal. 2003 ; Vol. 22, No. 16. pp. 4237-4248.
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