Nuclear export of NF90 to stabilize IL-2 mRNA is mediated by AKT-dependent phosphorylation at Ser647 in response to CD28 costimulation

Yuan Pei, Ping Zhu, Yongjun Dang, Jiaxue Wu, Xianmei Yang, Bo Wan, Jun Liu, Qing Yi, Long Yu

Research output: Contribution to journalArticle

Abstract

IL-2 is one of the most important cytokines required for T cell-mediated immune responses. Costimulation of CD28 in T cells up-regulates IL-2 mRNA levels via transcription activation and mRNA stabilization. Upon T cell activation, NF90, an AU-rich element (ARE)-binding protein, translocates from the nucleus into the cytoplasm, where it binds to the ARE-containing 3′ untranslated regions of IL-2 mRNA and slows down degradation of IL-2 mRNA. The translocation of NF90 is mediated through a nuclear export signal at its N terminus, but how it is triggered is still unclear. Phosphorylation of ARE-binding proteins has been reported as a signal transduction pathway to stabilize ARE-containing transcripts. In this study, we demonstrate that AKT phosphorylates NF90 on Ser647 upon CD28 costimulation. This phosphorylation is necessary for nuclear export of NF90 and IL-2 mRNA stabilization by this protein, because a mutation at Ser647 abolished both functions. We observed that treatment of cells with CD28 costimulation induced distinct increase in phosphorylation of AKT and NF90 at Ser647 concomitantly. Phosphorylation at Ser647 of NF90 up-regulated IL-2 production in response to CD28 costimulation. In vivo and in vitro data support a model in which CD28 costimulation activates AKT to phosphorylate NF90 at Ser 647 and phosphorylation triggers NF90 to relocate to the cytoplasm and stabilize IL-2 mRNA.

Original languageEnglish (US)
Pages (from-to)222-229
Number of pages8
JournalJournal of Immunology
Volume180
Issue number1
StatePublished - Jan 1 2008

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Cell Nucleus Active Transport
Interleukin-2
AU Rich Elements
Phosphorylation
Messenger RNA
T-Lymphocytes
Carrier Proteins
Cytoplasm
Nuclear Export Signals
3' Untranslated Regions
Transcriptional Activation
Signal Transduction
Up-Regulation
Cytokines
Mutation

ASJC Scopus subject areas

  • Immunology

Cite this

Nuclear export of NF90 to stabilize IL-2 mRNA is mediated by AKT-dependent phosphorylation at Ser647 in response to CD28 costimulation. / Pei, Yuan; Zhu, Ping; Dang, Yongjun; Wu, Jiaxue; Yang, Xianmei; Wan, Bo; Liu, Jun; Yi, Qing; Yu, Long.

In: Journal of Immunology, Vol. 180, No. 1, 01.01.2008, p. 222-229.

Research output: Contribution to journalArticle

Pei, Yuan ; Zhu, Ping ; Dang, Yongjun ; Wu, Jiaxue ; Yang, Xianmei ; Wan, Bo ; Liu, Jun ; Yi, Qing ; Yu, Long. / Nuclear export of NF90 to stabilize IL-2 mRNA is mediated by AKT-dependent phosphorylation at Ser647 in response to CD28 costimulation. In: Journal of Immunology. 2008 ; Vol. 180, No. 1. pp. 222-229.
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AU - Yang, Xianmei

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