KEGG   PATHWAY: oaa04960Help
Entry
oaa04960                    Pathway                                

Name
Aldosterone-regulated sodium reabsorption - Ornithorhynchus anatinus (platypus)
Description
Sodium transport across the tight epithelia of Na+ reabsorbing tissues such as the distal part of the kidney nephron and colon is the major factor determining total-body Na+ levels, and thus, long-term blood pressure. Aldosterone plays a major role in sodium and potassium metabolism by binding to epithelial mineralocorticoid receptors (MR) in the renal collecting duct cells localized in the distal nephron, promoting sodium resorption and potassium excretion. Aldosterone enters a target cell and binds MR, which translocates into the nucleus and regulates gene transcription. Activation of MR leads to increased expression of Sgk-1, which phosphorylates Nedd4-2, an ubiquitin-ligase which targets ENAC to proteosomal degradation. Phosphorylated Nedd4-2 dissociates from ENAC, increasing its apical membrane abundance. Activation of MR also leads to increased expression of Na+/K+-ATPase, thus causing a net increase in sodium uptake from the renal filtrate. The specificity of MR for aldosterone is provided by 11beta-HSD2 by the rapid conversion of cortisol to cortisone in renal cortical collecting duct cells. Recently, besides genomic effects mediated by activated MR, rapid aldosterone actions that are independent of translation and transcription have been documented.
Class
Organismal Systems; Excretory system
BRITE hierarchy
Pathway map
Aldosterone-regulated sodium reabsorption
oaa04960

All organismsOrtholog table
Organism
Ornithorhynchus anatinus (platypus) [GN:oaa]
Gene
corticosteroid 11-beta-dehydrogenase isozyme 2-like; K00071 corticosteroid 11-beta-dehydrogenase isozyme 2 [EC:1.1.1.-] [KO:K00071] [EC:1.1.1.-]
mineralocorticoid receptor-like; K08555 mineralocorticoid receptor [KO:K08555]
SCNN1A; sodium channel, non-voltage-gated 1 alpha subunit [KO:K04824]
SCNN1B; sodium channel, non-voltage-gated 1, beta subunit [KO:K04825]
amiloride-sensitive sodium channel subunit gamma-like; K04827 amiloride-sensitive sodium channel subunit gamma [KO:K04827]
SGK1; serum/glucocorticoid regulated kinase 1 [KO:K13302] [EC:2.7.11.1]
ATP-sensitive inward rectifier potassium channel 1-like; K04995 potassium inwardly-rectifying channel subfamily J member 1 [KO:K04995]
14-3-3 protein sigma-like; K06644 stratifin [KO:K06644]
GTPase KRas-like; K07827 GTPase KRas [KO:K07827]
sodium/potassium-transporting ATPase subunit beta-1-like; K01540 sodium/potassium-transporting ATPase subunit beta [KO:K01540]
sodium/potassium-transporting ATPase subunit beta-3-like; K01540 sodium/potassium-transporting ATPase subunit beta [KO:K01540]
protein ATP1B4-like; K01540 sodium/potassium-transporting ATPase subunit beta [KO:K01540]
insulin-like growth factor I-like; K05459 insulin-like growth factor 1 [KO:K05459]
INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
insulin receptor substrate 1-like; K16172 insulin receptor substrate 1 [KO:K16172]
phosphoinositide 3-kinase regulatory subunit 5-like; K02649 phosphoinositide-3-kinase, regulatory subunit [KO:K02649]
PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
phosphatidylinositol 3-kinase regulatory subunit alpha-like; K02649 phosphoinositide-3-kinase, regulatory subunit [KO:K02649]
phosphatidylinositol 3-kinase regulatory subunit gamma-like; K02649 phosphoinositide-3-kinase, regulatory subunit [KO:K02649]
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
phosphatidylinositol-4; K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153] [KO:K00922] [EC:2.7.1.153]
phosphatidylinositol-4; K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153] [KO:K00922] [EC:2.7.1.153]
3-phosphoinositide-dependent protein kinase 1-like; K06276 3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1] [KO:K06276] [EC:2.7.11.1]
protein kinase C alpha type-like; K02677 classical protein kinase C [EC:2.7.11.13] [KO:K02677] [EC:2.7.11.13]
mitogen-activated protein kinase 1-like; K04371 extracellular signal-regulated kinase 1/2 [EC:2.7.11.24] [KO:K04371] [EC:2.7.11.24]
Compound
C00238  
Potassium cation
C00575  
3',5'-Cyclic AMP
C00698  
Cl-
C00735  
Cortisol
C00762  
Cortisone
C01330  
Sodium cation
C01780  
Aldosterone
C05981  
Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Connell JM, Davies E
  Title
The new biology of aldosterone.
  Journal
J Endocrinol 186:1-20 (2005)
Reference
  Authors
Booth RE, Johnson JP, Stockand JD
  Title
Aldosterone.
  Journal
Adv Physiol Educ 26:8-20 (2002)
Reference
  Authors
Lee IH, Campbell CR, Cook DI, Dinudom A
  Title
Regulation of epithelial Na+ channels by aldosterone: role of Sgk1.
  Journal
Clin Exp Pharmacol Physiol 35:235-41 (2008)
Reference
  Authors
Viengchareun S, Le Menuet D, Martinerie L, Munier M, Pascual-Le Tallec L, Lombes M
  Title
The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology.
  Journal
Nucl Recept Signal 5:e012 (2007)
Reference
  Authors
Fuller PJ, Young MJ
  Title
Mechanisms of mineralocorticoid action.
  Journal
Hypertension 46:1227-35 (2005)
Reference
  Authors
Verrey F, Loffing J, Zecevic M, Heitzmann D, Staub O
  Title
SGK1: aldosterone-induced relay of Na+ transport regulation in distal kidney nephron cells.
  Journal
Cell Physiol Biochem 13:21-8 (2003)
Reference
  Authors
Pearce D, Kleyman TR
  Title
Salt, sodium channels, and SGK1.
  Journal
J Clin Invest 117:592-5 (2007)
Reference
  Authors
Grossmann C, Gekle M
  Title
New aspects of rapid aldosterone signaling.
  Journal
Mol Cell Endocrinol 308:53-62 (2009)
Reference
  Authors
Vallon V, Wulff P, Huang DY, Loffing J, Volkl H, Kuhl D, Lang F
  Title
Role of Sgk1 in salt and potassium homeostasis.
  Journal
Am J Physiol Regul Integr Comp Physiol 288:R4-10 (2005)
Reference
  Authors
Rogerson FM, Brennan FE, Fuller PJ
  Title
Dissecting mineralocorticoid receptor structure and function.
  Journal
J Steroid Biochem Mol Biol 85:389-96 (2003)
Reference
  Authors
Wang J, Barbry P, Maiyar AC, Rozansky DJ, Bhargava A, Leong M, Firestone GL, Pearce D
  Title
SGK integrates insulin and mineralocorticoid regulation of epithelial sodium transport.
  Journal
Am J Physiol Renal Physiol 280:F303-13 (2001)
Reference
  Authors
Good DW
  Title
Nongenomic actions of aldosterone on the renal tubule.
  Journal
Hypertension 49:728-39 (2007)
KO pathway
 

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