Molecular requirements for the regulation of the renal outer medullary K(+) channel ROMK1 by the serum- and glucocorticoid-inducible kinase SGK1.
The serum- and glucocorticoid- inducible kinase SGK1 stimulates the renal outer medullary K(+) channel ROMK1 in the presence of the Na(+)/H(+) exchanger regulating factor NHERF2. SGK1/NHERF2 are effective through enhancement of ROMK1 abundance within the cell membrane. The present study aims to define the molecular requirements for the interaction of ROMK1 with SGK1/NHERF2. Pull down assays reveal that SGK1 interacts with NHERF2 through the second PDZ domain of NHERF2. According to chemiluminescence and electrophysiology, deletion of the second PDZ domain of NHERF2 or the putative PDZ binding motif on ROMK1 abrogates the stimulating effect of SGK1 on ROMK1 protein abundance in the plasma membrane and K(+) current.
Palmada
Monica
M
Department of Physiology I, University of Tübingen, Gmelinstr 5, 72076 Tübingen, Germany.
Embark
Hamdy M
HM
Yun
Chris
C
Böhmer
Christoph
C
Lang
Florian
F
D000450:Aldosterone / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins; D007668:Kidney / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010750:Phosphoproteins; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017923:Sodium-Hydrogen Exchangers; D014982:Xenopus laevis; D000099184:Serum-Glucocorticoid Regulated Kinases
D000450:Aldosterone; D003598:Cytoskeletal Proteins; D005982:Glutathione Transferase; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011188:Potassium; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D017346:Protein Serine-Threonine Kinases; D017923:Sodium-Hydrogen Exchangers; D000099184:Serum-Glucocorticoid Regulated Kinases; C086989:KCNJ1 protein, human; C093376:sodium-hydrogen exchanger regulatory factor