KEGG   PATHWAY: ko04960Help
Entry
ko04960                     Pathway                                

Name
Aldosterone-regulated sodium reabsorption
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
ko04960

All organismsOrtholog table
Disease
H00239  
Bartter syndrome
H00242  
Liddle syndrome
H00243  
Hyperkalemic distal renal tubular acidosis (RTA type 4)
H00603  
Hypertension exacerbated in pregnancy
H00719  
Leprechaunism
H00892  
Bronchiectasis with or without elevated sweat chloride
H00942  
Rabson-Mendenhall syndrome
H00998  
Alternating hemiplegia of childhood
H01228  
Insulin-resistant diabetes mellitus with acanthosis nigricans (IRAN)
Orthology
K00071  
corticosteroid 11-beta-dehydrogenase isozyme 2 [EC:1.1.1.-]
K08555  
mineralocorticoid receptor
K04824  
amiloride-sensitive sodium channel subunit alpha
K04825  
amiloride-sensitive sodium channel subunit beta
K04827  
amiloride-sensitive sodium channel subunit gamma
K13302  
serum/glucocorticoid-regulated kinase 1 [EC:2.7.11.1]
K04995  
potassium inwardly-rectifying channel subfamily J member 1
K13358  
Na(+)/H(+) exchange regulatory cofactor NHE-RF2
K13305  
E3 ubiquitin-protein ligase NEDD4-like [EC:6.3.2.19]
K06644  
stratifin
K07827  
GTPase KRas
K01539  
sodium/potassium-transporting ATPase subunit alpha [EC:3.6.3.9]
K01540  
sodium/potassium-transporting ATPase subunit beta
K01538  
sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2)
K13359  
FXYD domain containing ion transport regulator 4
K04526  
insulin
K05459  
insulin-like growth factor 1
K04527  
insulin receptor [EC:2.7.10.1]
K16172  
insulin receptor substrate 1
K02649  
phosphoinositide-3-kinase, regulatory subunit
K00922  
phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153]
K06276  
3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1]
K02677  
classical protein kinase C [EC:2.7.11.13]
K04371  
mitogen-activated protein kinase 1/3 [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)

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