New ideas about aldosterone signaling in epithelia.
The systemic actions of aldosterone are well documented; however, in comparison, our understanding of the cellular and molecular mechanisms by which aldosterone orchestrates these actions is rudimentary. Aldosterone exerts most of its physiological actions by modifying gene expression. It is now apparent that aldosterone represses almost as many genes as it induces. Several aldosterone-sensitive genes, including serum and glucocorticoid-inducible kinase (sgk) and small, monomeric Kirsten Ras GTP-binding protein (Ki-ras) have recently been identified. The molecular mechanisms and elements bestowing corticosteroid sensitivity on these and many other genes are becoming clear. Induction of Ki-Ras and Sgk is necessary and sufficient for some portion of aldosterone action in epithelia. These two signaling factors are components of a converging pathway with phosphatidylinositol 3-kinase positioned between them that enables both stabilizing the epithelial Na(+) channel (ENaC) in the open state as well as increasing the number of ENaC in the apical membrane. This aldosterone-induced signaling pathway contains many potential sites for feedback regulation and cross talk from other cascades and potentially impinges directly on the activity of transport proteins and/or cellular differentiation to modify electrolyte transport.
Stockand
James D
JD
Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio Texas 78229-3900, USA. stockand@uthscsa.edu
D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D004847:Epithelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*
D002352:Carrier Proteins; D011506:Proteins; D000450:Aldosterone