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Nat Immunol. 2004 Feb;5(2):208-15. Epub 2004 Jan 4.

N-domain-dependent nonphosphorylated STAT4 dimers required for cytokine-driven activation.

Author information

1
Department of Pathology & Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110, USA.

Abstract

The N-terminal protein interaction domain (N-domain) of the signal transducer and activator of transcription-4 (STAT4) is believed to stabilize interactions between two phosphorylated STAT4 dimers to form STAT4 tetramers. Here, we show that nonphosphorylated STAT4 dimers form in vivo before cytokine receptor-driven activation. Mutations in the N-domain dimerization interface abolished assembly of nonphosphorylated STAT4 dimers and prevented STAT4 phosphorylation mediated by cytokine receptors. In addition, N-domain dimerization occurred for other STAT family members but was homotypic in character. This implies a conserved role for N-domain dimerization, which might include influencing interactions with cytokine receptors, favoring homodimer formation or accelerating formation of the phosphorylated STAT dimer.

PMID:
14704793
DOI:
10.1038/ni1032
[Indexed for MEDLINE]

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