Brx mediates the response of lymphocytes to osmotic stress through the activation of NFAT5

Tomoshige Kino, Hiroaki Takatori, Irini Manoli, Yonghong Wang, Anatoly Tiulpakov, Marc R. Blackman, Yan A. Su, George P. Chrousos, Alan H. DeCherney, James H. Segars

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Extracellular hyperosmolarity, or osmotic stress, generally caused by differences in salt and macro-molecule concentrations across the plasma membrane, occurs in lymphoid organs and at inflammatory sites. The response of immune cells to osmotic stress is regulated by nuclear factor of activated T cells 5 (NFAT5), a transcription factor that induces the expression of hyperosmolarity-responsive genes and stimulates cytokine production. We report that the guanine nucleotide exchange factor (GEF) Brx [also known as protein kinase A-anchoring protein 13 (AKAP13)] is essential for the expression of nfat5 in response to osmotic stress, thus transmitting the extracellular hyperosmolarity signal and enabling differentiation of splenic B cells and production of immunoglobulin. This process required the activity of p38 mitogen-activated protein kinase (MAPK) and NFAT5 and involved a physical interaction between Brx and c-Jun N-terminal kinase (JNK)-interacting protein 4 (JIP4), a scaffold molecule specific to activation of the p38 MAPK cascade. Our results indicate that Brx integrates the responses of immune cells to osmotic stress and inflammation by elevating intracellular osmolarity and stimulating the production of cytokines.

Original languageEnglish
JournalScience Signaling
Volume2
Issue number57
DOIs
Publication statusPublished - 10 Feb 2009
Externally publishedYes

Fingerprint

NFATC Transcription Factors
Lymphocytes
Osmotic Pressure
Chemical activation
p38 Mitogen-Activated Protein Kinases
Cytokines
Guanine Nucleotide Exchange Factors
Osmoregulation
JNK Mitogen-Activated Protein Kinases
Cyclic AMP-Dependent Protein Kinases
Osmolar Concentration
Molecules
Immunoglobulins
Proteins
B-Lymphocytes
Transcription Factors
Cell membranes
Salts
Cell Membrane
Scaffolds

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kino, T., Takatori, H., Manoli, I., Wang, Y., Tiulpakov, A., Blackman, M. R., ... Segars, J. H. (2009). Brx mediates the response of lymphocytes to osmotic stress through the activation of NFAT5. Science Signaling, 2(57). https://doi.org/10.1126/scisignal.2000081

Brx mediates the response of lymphocytes to osmotic stress through the activation of NFAT5. / Kino, Tomoshige; Takatori, Hiroaki; Manoli, Irini; Wang, Yonghong; Tiulpakov, Anatoly; Blackman, Marc R.; Su, Yan A.; Chrousos, George P.; DeCherney, Alan H.; Segars, James H.

In: Science Signaling, Vol. 2, No. 57, 10.02.2009.

Research output: Contribution to journalArticle

Kino, T, Takatori, H, Manoli, I, Wang, Y, Tiulpakov, A, Blackman, MR, Su, YA, Chrousos, GP, DeCherney, AH & Segars, JH 2009, 'Brx mediates the response of lymphocytes to osmotic stress through the activation of NFAT5', Science Signaling, vol. 2, no. 57. https://doi.org/10.1126/scisignal.2000081
Kino, Tomoshige ; Takatori, Hiroaki ; Manoli, Irini ; Wang, Yonghong ; Tiulpakov, Anatoly ; Blackman, Marc R. ; Su, Yan A. ; Chrousos, George P. ; DeCherney, Alan H. ; Segars, James H. / Brx mediates the response of lymphocytes to osmotic stress through the activation of NFAT5. In: Science Signaling. 2009 ; Vol. 2, No. 57.
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