Recruitment of the extracellular signal-regulated kinase/ribosomal S6 kinase signaling pathway to the NFATc4 transcription activation complex

Teddy T C Yang, Qiufang Xiong, Isabella A. Graef, Gerald R. Crabtree, Chi Wing Chow

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Integration of protein kinases into transcription activation complexes influences the magnitude of gene expression. The nuclear factor of activated T cells (NFAT) group of proteins are critical transcription factors that direct gene expression in immune and nonimmune cells. A balance of phosphotransferase activity is necessary for optimal NFAT activation. Activation of NFAT requires dephosphorylation by the calcium-mediated calcineurin phosphatase to promote NFAT nuclear accumulation, and the Ras-activated extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase, which targets NFAT partners, to potentiate transcription. Whether protein kinases operate on NFAT and contribute positively to transcription activation is not clear. Here, we coupled DNA affinity isolation with in-gel kinase assays to avidly pull down the activated NFAT and identify its associated protein kinases. We demonstrate that p90 ribosomal S6 kinase (RSK) is recruited to the NFAT-DNA transcription complex upon activation. The formation of RSK-NFATc4-DNA transcription complex is also apparent upon adipogenesis. Bound RSK phosphorylates Ser676 and potentiates NFATc4 DNA binding by escalating NFAT-DNA association. Ser 676 is also targeted by the ERK MAP kinase, which interacts with NFAT at a distinct region than RSK. Thus, integration of the ERK/RSK signaling pathway provides a mechanism to modulate NFATc4 transcription activity.

Original languageEnglish (US)
Pages (from-to)907-920
Number of pages14
JournalMolecular and Cellular Biology
Volume25
Issue number3
DOIs
StatePublished - Feb 2005

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Ribosomal Protein S6 Kinases
NFATC Transcription Factors
Extracellular Signal-Regulated MAP Kinases
Transcriptional Activation
Protein Kinases
Mitogen-Activated Protein Kinases
DNA
90-kDa Ribosomal Protein S6 Kinases
Phosphotransferases
Gene Expression
Adipogenesis
Transcription Factors
Gels

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Recruitment of the extracellular signal-regulated kinase/ribosomal S6 kinase signaling pathway to the NFATc4 transcription activation complex. / Yang, Teddy T C; Xiong, Qiufang; Graef, Isabella A.; Crabtree, Gerald R.; Chow, Chi Wing.

In: Molecular and Cellular Biology, Vol. 25, No. 3, 02.2005, p. 907-920.

Research output: Contribution to journalArticle

Yang, Teddy T C ; Xiong, Qiufang ; Graef, Isabella A. ; Crabtree, Gerald R. ; Chow, Chi Wing. / Recruitment of the extracellular signal-regulated kinase/ribosomal S6 kinase signaling pathway to the NFATc4 transcription activation complex. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 3. pp. 907-920.
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