STAT4 requires the N-terminal domain for efficient phosphorylation

Hua Chen Chang, Shangming Zhang, India Oldham, Lisa Naeger, Timothy Hoey, Mark H. Kaplan

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

STAT4 (signal transducer and activator of transcription-4) mediates biological effects in response to interleukin-12 (IL-12). STAT4 has multiple domains that have distinct functions in signaling and gene activation. To characterize the role of the STAT4 N-terminal domain in mediating STAT4 biological function, we have generated STAT4-deficient transgenic mice that express human full-length STAT4 or an N-terminal deletion mutant (AN-STAT4) lacking the N-terminal 51 amino acids. Whereas full-length STAT4 rescued IL-12 responsiveness, T lymphocytes expressing the STAT4 N-terminal mutant failed to proliferate in response to IL-12 and had limited Thl cell development as evidenced by minimal interferon-γ production. Deletion of the N-terminal domain resulted in failure of STAT4 to be phosphorylated following IL-12 stimulation despite similar phosphorylation of JAK2 and TYK2 in full-length STAT4 and ΔN-STAT4 transgenic T cells. We demonstrate that the lack of phosphorylation in cultured cells is due to reduced efficiency of phosphorylation of ΔN-STAT4 by Janus kinases. These data support a new model wherein the N-terminal domain is required to mediate the phosphorylation of STAT4 in addition to the previously documented role in gene transactivation.

Original languageEnglish (US)
Pages (from-to)32471-32477
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number34
DOIs
StatePublished - Aug 22 2003

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STAT4 Transcription Factor
Phosphorylation
Interleukin-12
T-cells
Transcriptional Activation
Genes
Janus Kinases
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chang, H. C., Zhang, S., Oldham, I., Naeger, L., Hoey, T., & Kaplan, M. H. (2003). STAT4 requires the N-terminal domain for efficient phosphorylation. Journal of Biological Chemistry, 278(34), 32471-32477. https://doi.org/10.1074/jbc.M302776200
Chang, Hua Chen ; Zhang, Shangming ; Oldham, India ; Naeger, Lisa ; Hoey, Timothy ; Kaplan, Mark H. / STAT4 requires the N-terminal domain for efficient phosphorylation. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 34. pp. 32471-32477.
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Chang, HC, Zhang, S, Oldham, I, Naeger, L, Hoey, T & Kaplan, MH 2003, 'STAT4 requires the N-terminal domain for efficient phosphorylation', Journal of Biological Chemistry, vol. 278, no. 34, pp. 32471-32477. https://doi.org/10.1074/jbc.M302776200

STAT4 requires the N-terminal domain for efficient phosphorylation. / Chang, Hua Chen; Zhang, Shangming; Oldham, India; Naeger, Lisa; Hoey, Timothy; Kaplan, Mark H.

In: Journal of Biological Chemistry, Vol. 278, No. 34, 22.08.2003, p. 32471-32477.

Research output: Contribution to journalArticle

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