Regulation of Human Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by Serum- and Glucocorticoid-Inducible Kinase (SGK1)
| Autor: | Renee Thibodeau, M. Christine Chapline, J. Denry Sato, Raymond A. Frizzell, Bruce A. Stanton |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Physiology Xenopus Voltage clamp Amino Acid Motifs Molecular Sequence Data PDZ domain Cystic Fibrosis Transmembrane Conductance Regulator In Vitro Techniques Protein Serine-Threonine Kinases Biology Immediate early protein Immediate-Early Proteins Cell membrane 1-Methyl-3-isobutylxanthine Fundulidae medicine Animals Humans Amino Acid Sequence Ion channel Sequence Homology Amino Acid urogenital system Cell Membrane respiratory system biology.organism_classification Molecular biology Recombinant Proteins digestive system diseases Cystic fibrosis transmembrane conductance regulator respiratory tract diseases Cell biology medicine.anatomical_structure Amino Acid Substitution Mutagenesis Site-Directed Oocytes SGK1 biology.protein Female |
| Zdroj: | Cellular Physiology and Biochemistry. 20:091-098 |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background: Serum- and glucocorticoid-inducible kinase-1 (SGK1) increases CFTR Cl currents in Xenopus oocytes by an unknown mechanism. Because SGK increases the plasma membrane expression of other ion channels, the goal of this paper was to test the hypothesis that SGK1 stimulates CFTR Cl currents by increasing the number of CFTR Cl channels in the plasma membrane. Methods: CFTR Cl currents were measured in Xenopus oocytes by the two-electrode voltage clamp technique, and CFTR in the plasma membrane was determined by laser scanning confocal microscopy. Results: wt-SGK1 stimulated CFTR Cl currents by 42% and increased the amount of CFTR in the plasma membrane by 35%. A kinase-dead SGK mutant (K127N) had a dominant-negative effect on CFTR, reducing CFTR Cl currents by 38%. In addition, deletion of the C-terminal PDZ-interacting motif (SGK1-ΔSFL) increased CFTR Cl currents by 108%. Thus, SGK1-ΔSFL was more effective than wt-SGK1 in stimulating CFTR Cl currents. Neither wt-SGK nor the K127N mutant had any effect on Cl currents in oocytes when expressed alone in the absence of CFTR. Conclusion: SGK1 stimulates CFTR Cl currents in Xenopus oocytes by increasing the number of channels in the plasma membrane. Moreover, the effect of SGK may be mediated by protein-protein interactions involving the PDZ interacting motif. |
| Databáze: | OpenAIRE |
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