PMID- 15586017
OWN - NLM
STAT- MEDLINE
DCOM- 20050519
LR  - 20211203
IS  - 1062-4821 (Print)
IS  - 1062-4821 (Linking)
VI  - 14
IP  - 1
DP  - 2005 Jan
TI  - New insights into the role of serum- and glucocorticoid-inducible kinase SGK1 in 
      the regulation of renal function and blood pressure.
PG  - 59-66
AB  - PURPOSE OF REVIEW: The serum and glucocorticoid inducible kinase 1 (SGK1) is 
      induced in the aldosterone sensitive distal nephron (ASDN) where it may stimulate 
      Na reabsorption, partly by inhibiting ubiquitin ligase Nedd4-2-mediated retrieval 
      of epithelial Na+ channel ENaC from the luminal membrane. We describe recent 
      advances in our understanding of SGK1 function in the regulation of renal 
      function and blood pressure. RECENT FINDINGS: Thiazolidinediones, i.e. activators 
      of peroxisome proliferator-activated receptor gamma (PPAR gamma), upregulate SGK1 
      and ENaC mRNA expression and increase cell-surface expression of ENaC alpha in a 
      human cortical-collecting-duct cell line. cAMP/protein kinase A can induce 
      phosphorylation and inhibition of Nedd4-2-independent of SGK1. Part of ENaC 
      stimulation by SGK1 appears dependent on a SGK1 consensus motif in ENaC alpha and 
      independent of Nedd4-2. SGK1-dependent upregulation of Na+ reabsorption in ASDN 
      contributes to upregulation of renal K+ excretion. In oocytes, SGK1 activates 
      various renal transport proteins including Na+/glucose cotransporter SGLT1, 
      Na+-coupled dicarboxylate transporter NaDC-1, epithelial Ca+ channel TRPV5, renal 
      outer medullary K+ channel ROMK and voltage gated K+ channels KCNE1/KCNQ1 and 
      Kv1.3. A variant of the SGK1 gene associates with increased blood pressure and 
      body mass index. SUMMARY: PPAR gamma activators may increase renal Na 
      reabsorption by stimulating SGK1 and ENaC. Nedd4-2 integrates influences of 
      cAMP/protein kinase A and SGK1. SGK1 can activate ENaC in part directly and 
      independent of Nedd4-2. K+ homeostasis requires SGK1-dependent Na+ reabsorption 
      in ASDN. SGK1 may affect renal transport mechanisms beyond Na+ reabsorption and 
      K+ secretion in ASDN. Polymorphisms of SGK1 may be relevant to the 
      pathophysiology of hypertension and other diseases.
FAU - Vallon, Volker
AU  - Vallon V
AD  - Department of Medicine, University of California San Diego & VA San Diego Health 
      Care System, CA 92161, USA. vvallon@ucsd.edu
FAU - Lang, Florian
AU  - Lang F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Curr Opin Nephrol Hypertens
JT  - Current opinion in nephrology and hypertension
JID - 9303753
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (PPAR gamma)
RN  - 0 (Sodium Channels)
RN  - 9NEZ333N27 (Sodium)
RN  - EC 2.3.2.26 (WWP2 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (serum-glucocorticoid regulated kinase)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Blood Pressure/*physiology
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Humans
MH  - Immediate-Early Proteins
MH  - Kidney Tubules, Distal/metabolism/*physiology
MH  - Nuclear Proteins/*metabolism
MH  - PPAR gamma/metabolism
MH  - Polymorphism, Genetic
MH  - Potassium/metabolism
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Sodium/metabolism
MH  - Sodium Channels/metabolism
MH  - Ubiquitin-Protein Ligases/metabolism
MH  - Up-Regulation
RF  - 71
EDAT- 2004/12/09 09:00
MHDA- 2005/05/20 09:00
CRDT- 2004/12/09 09:00
PHST- 2004/12/09 09:00 [pubmed]
PHST- 2005/05/20 09:00 [medline]
PHST- 2004/12/09 09:00 [entrez]
AID - 00041552-200501000-00010 [pii]
AID - 10.1097/00041552-200501000-00010 [doi]
PST - ppublish
SO  - Curr Opin Nephrol Hypertens. 2005 Jan;14(1):59-66. doi: 
      10.1097/00041552-200501000-00010.