TAZ suppresses NFAT5 activity through tyrosine phosphorylation

Eun Jung Jang, Hana Jeong, Ki Hwan Han, Hyug Moo Kwon, Jeong-Ho Hong, Eun Sook Hwang

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Transcriptional coactivator with PDZ-binding motif (TAZ) physically interacts with a variety of transcription factors and modulates their activities involved in cell proliferation and mesenchymal stem cell differentiation. TAZ is highly expressed in the kidney, and a deficiency of this protein results in multiple renal cysts and urinary concentration defects; however, the molecular functions of TAZ in renal cells remain largely unknown. In this study, we examined the effects of osmotic stress on TAZ expression and activity in renal cells. We found that hyperosmotic stress selectively increased protein phosphorylation at tyrosine 316 of TAZ and that this was enhanced by c-Abl activation in response to hyperosmotic stress. Interestingly, phosphorylated TAZ physically interacted with nuclear factor of activated T cells 5 (NFAT5), a major osmoregulatory transcription factor, and subsequently suppressed DNA binding and transcriptional activity of NFAT5. Furthermore, TAZ deficiency elicited an increase in NFAT5 activity in vitro and in vivo, which then reverted to basal levels following restoration of wild-type TAZ but not mutant TAZ (Y316F). Collectively, the data suggest that TAZ modulates cellular responses to hyperosmotic stress through fine-tuning of NFAT5 activity via tyrosine phosphorylation.

Original languageEnglish
Pages (from-to)4925-4932
Number of pages8
JournalMolecular and Cellular Biology
Volume32
Issue number24
DOIs
Publication statusPublished - 2012 Dec 1

Fingerprint

NFATC Transcription Factors
Tyrosine
Phosphorylation
Kidney
Transcription Factors
Protein Deficiency
Osmotic Pressure
Mesenchymal Stromal Cells
Cysts
Cell Differentiation
Cell Proliferation
DNA
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Jang, E. J., Jeong, H., Han, K. H., Kwon, H. M., Hong, J-H., & Hwang, E. S. (2012). TAZ suppresses NFAT5 activity through tyrosine phosphorylation. Molecular and Cellular Biology, 32(24), 4925-4932. https://doi.org/10.1128/MCB.00392-12

TAZ suppresses NFAT5 activity through tyrosine phosphorylation. / Jang, Eun Jung; Jeong, Hana; Han, Ki Hwan; Kwon, Hyug Moo; Hong, Jeong-Ho; Hwang, Eun Sook.

In: Molecular and Cellular Biology, Vol. 32, No. 24, 01.12.2012, p. 4925-4932.

Research output: Contribution to journalArticle

Jang, EJ, Jeong, H, Han, KH, Kwon, HM, Hong, J-H & Hwang, ES 2012, 'TAZ suppresses NFAT5 activity through tyrosine phosphorylation', Molecular and Cellular Biology, vol. 32, no. 24, pp. 4925-4932. https://doi.org/10.1128/MCB.00392-12
Jang, Eun Jung ; Jeong, Hana ; Han, Ki Hwan ; Kwon, Hyug Moo ; Hong, Jeong-Ho ; Hwang, Eun Sook. / TAZ suppresses NFAT5 activity through tyrosine phosphorylation. In: Molecular and Cellular Biology. 2012 ; Vol. 32, No. 24. pp. 4925-4932.
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