Brx, a link between osmotic stress, inflammation and organ physiology/pathophysiology

Tomoshige Kino, James H. Segars, George P. Chrousos

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

Dehydration, and consequent intracellular hyperosmolarity, is a major challenge to land organisms as it is associated with extraction of water from cells and disturbance of global cellular function. Organisms have thus developed a highly conserved regulatory mechanism that transduces the hyperosmolarity signal from the cell surface to the cell nucleus and adjusts the expression of cellular osmolarity-regulating genes. We recently found that the Rho-type guanine nucleotide exchange factor Brx, or AKAP13, is essential for osmotic stress-stimulated expression of nuclear factor of activated T cells 5 (NFAT5), a key transcription factor of intracellular osmolarity. It accomplishes this by first attracting cJun kinase-interacting protein 4 and then coupling activated Rho-type small G-proteins to cascade components of the p38 MAPK signaling pathway, ultimately activating NFAT5. We describe the potential implications of osmotic stress and Brx activation in organ physiology and pathophysiology and connect activation of this system to key human homeostatic states.

Original languageEnglish
Pages (from-to)603-614
Number of pages12
JournalExpert Review of Endocrinology and Metabolism
Volume5
Issue number4
DOIs
Publication statusPublished - 1 Jul 2010

    Fingerprint

Keywords

  • cJun kinase-interacting protein
  • glucocorticoid receptor
  • glucocorticoids
  • guanine nucleotide exchange factor
  • hyperosmolarity
  • mitogen-activated protein kinase
  • nuclear factor of activated T cells 5
  • smallGTP-binding protein

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this