KEGG   PATHWAY: ncar04925
Entry
ncar04925                   Pathway                                
Name
Aldosterone synthesis and secretion - Sciurus carolinensis (gray squirrel)
Description
Aldosterone is a steroid hormone synthesized in and secreted from the outer layer of the adrenal cortex, the zona glomerulosa. Aldosterone plays an important role in the regulation of systemic blood pressure through the absorption of sodium and water. Angiotensin II (Ang II), potassium (K+) and adrenocorticotropin (ACTH) are the main extracellular stimuli which regulate aldosterone secretion. These physiological agonists all converge on two major intracellular signaling pathways: calcium (Ca2+) mobilization and an increase in cAMP production. The increase in cytosolic calcium levels activates calcium/calmodulin- dependent protein kinases (CaMK), and the increased cAMP levels stimulate the activity of cAMP-dependent protein kinase, or protein kinase A (PKA). The activated CaMK, and possibly PKA, activates transcription factors (NURR1 and NGF1B, CREB) to induce StAR and CYP11B2 expression, the early and late rate- limiting steps in aldosterone biosynthesis, respectively, thereby stimulating aldosterone secretion.
Class
Organismal Systems; Endocrine system
Pathway map
ncar04925  Aldosterone synthesis and secretion
ncar04925

Other DBs
GO: 0035932
Organism
Sciurus carolinensis (gray squirrel) [GN:ncar]
Gene
124961133  angiotensinogen-like [KO:K09821]
124992863  type-1 angiotensin II receptor [KO:K04166]
124964255  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
124968563  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
124976705  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
124959812  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
124977474  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
124972679  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
124970932  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
124983533  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
124988553  inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
124979014  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
124970211  LOW QUALITY PROTEIN: protein kinase C beta type-like [KO:K19662] [EC:2.7.11.13]
124967611  protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
124962983  protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
124967388  serine/threonine-protein kinase D2 [KO:K06070] [EC:2.7.11.13]
124977304  serine/threonine-protein kinase D1 isoform X1 [KO:K06070] [EC:2.7.11.13]
124962988  serine/threonine-protein kinase D3 isoform X1 [KO:K06070] [EC:2.7.11.13]
124979032  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
124979831  LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2-like [KO:K04450]
124984025  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
124991113  cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
124958938  cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
124984689  cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
124969564  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
124964377  cyclic AMP-responsive element-binding protein 3-like isoform X1 [KO:K09048]
124991182  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
124988573  cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
124983318  cyclic AMP-dependent transcription factor ATF-1 isoform X1 [KO:K09053]
124960414  diacylglycerol lipase-alpha [KO:K13806] [EC:3.1.1.116]
124970633  diacylglycerol lipase-beta [KO:K13806] [EC:3.1.1.116]
124963245  potassium channel subfamily K member 3 [KO:K04914]
124964494  potassium channel subfamily K member 9 [KO:K04919]
124960772  G protein-activated inward rectifier potassium channel 4 isoform X1 [KO:K04999]
124967385  sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
124979517  sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
124981180  LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-1-like [KO:K01539] [EC:7.2.2.13]
124992537  sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540]
124961571  sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
124981128  sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
124972490  protein ATP1B4 isoform X1 [KO:K01540]
124979221  voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
124970247  LOW QUALITY PROTEIN: voltage-dependent T-type calcium channel subunit alpha-1H-like [KO:K04855]
124982472  voltage-dependent T-type calcium channel subunit alpha-1I isoform X1 [KO:K04856]
124982084  voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
124968359  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04851]
124971751  voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
124961645  voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
124990787  calcium release-activated calcium channel protein 1 isoform X1 [KO:K16056]
124976834  LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
124967357  calmodulin-1 [KO:K02183]
124967948  calmodulin-like protein 6 [KO:K02183]
124962006  calmodulin-like [KO:K02183]
124962112  calmodulin-A-like [KO:K02183]
124962222  calmodulin-like protein 3 [KO:K02183]
124963056  calmodulin-1 [KO:K02183]
124976085  calmodulin-1 [KO:K02183]
124961680  calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
124961928  calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
124971021  calcium/calmodulin-dependent protein kinase type 1 [KO:K08794] [EC:2.7.11.17]
124985817  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
124986742  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
124994412  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
124990768  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
124987181  calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
124962398  plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
124970941  plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
124971750  plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
124983674  plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
124966648  hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
124968885  low-density lipoprotein receptor-like [KO:K12473]
124990716  scavenger receptor class B member 1 isoform X1 [KO:K13885]
124963358  pro-opiomelanocortin-like [KO:K05228]
124965743  adrenocorticotropic hormone receptor-like [KO:K04200]
124978161  neuroendocrine secretory protein 55 [KO:K04632]
124975134  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
124990345  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
124987010  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
124962927  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
124978229  LOW QUALITY PROTEIN: adenylate cyclase type 4-like [KO:K08044] [EC:4.6.1.1]
124992559  adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
124983776  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
124966834  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
124965096  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
124970113  LOW QUALITY PROTEIN: adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
124985819  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
124969119  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
124983155  steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
124980303  LOW QUALITY PROTEIN: nuclear receptor subfamily 4 group A member 2-like [KO:K08558]
124982326  nuclear receptor subfamily 4 group A member 1 [KO:K04465]
124977503  cholesterol side-chain cleavage enzyme, mitochondrial-like isoform X1 [KO:K00498] [EC:1.14.15.6]
124992819  LOW QUALITY PROTEIN: 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
124990189  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
124964015  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase-like isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
124988309  steroid 21-hydroxylase-like isoform X1 [KO:K00513] [EC:1.14.14.16]
124963564  natriuretic peptides A-like [KO:K12334]
124961045  atrial natriuretic peptide receptor 1 isoform X1 [KO:K12323] [EC:4.6.1.2]
124959840  cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X1 [KO:K18283] [EC:3.1.4.17]
Compound
C00003  NAD+
C00004  NADH
C00005  NADPH
C00006  NADP+
C00020  AMP
C00076  Calcium cation
C00165  Diacylglycerol
C00187  Cholesterol
C00219  Arachidonate
C00238  Potassium cation
C00410  Progesterone
C00575  3',5'-Cyclic AMP
C00942  3',5'-Cyclic GMP
C01124  18-Hydroxycorticosterone
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01780  Aldosterone
C01953  Pregnenolone
C02140  Corticosterone
C03205  11-Deoxycorticosterone
C14777  12(S)-HETE
C14822  12(R)-HETE
Reference
PMID:21839803
  Authors
Hattangady NG, Olala LO, Bollag WB, Rainey WE
  Title
Acute and chronic regulation of aldosterone production.
  Journal
Mol Cell Endocrinol 350:151-62 (2012)
DOI:10.1016/j.mce.2011.07.034
Reference
PMID:24944029
  Authors
Bollag WB
  Title
Regulation of aldosterone synthesis and secretion.
  Journal
Compr Physiol 4:1017-55 (2014)
DOI:10.1002/cphy.c130037
Reference
PMID:15044681
  Authors
Spat A, Hunyady L
  Title
Control of aldosterone secretion: a model for convergence in cellular signaling pathways.
  Journal
Physiol Rev 84:489-539 (2004)
DOI:10.1152/physrev.00030.2003
Reference
PMID:18406824
  Authors
Boon WC, Coghlan JP, Curnow KM, McDougall JG
  Title
Aldosterone secretion: a molecular perspective.
  Journal
Trends Endocrinol Metab 8:346-54 (1997)
DOI:10.1016/S1043-2760(97)00136-7
Reference
PMID:14645496
  Authors
Bassett MH, Suzuki T, Sasano H, White PC, Rainey WE
  Title
The orphan nuclear receptors NURR1 and NGFIB regulate adrenal aldosterone production.
  Journal
Mol Endocrinol 18:279-90 (2004)
DOI:10.1210/me.2003-0005
Reference
PMID:22689262
  Authors
Guagliardo NA, Yao J, Hu C, Barrett PQ
  Title
Minireview: aldosterone biosynthesis: electrically gated for our protection.
  Journal
Endocrinology 153:3579-86 (2012)
DOI:10.1210/en.2012-1339
Reference
PMID:22364774
  Authors
Spat A, Fulop L, Szanda G
  Title
The role of mitochondrial Ca(2+) and NAD(P)H in the control of aldosterone secretion.
  Journal
Cell Calcium 52:64-72 (2012)
DOI:10.1016/j.ceca.2012.01.009
Reference
PMID:22395411
  Authors
Spat A, Szanda G
  Title
Special features of mitochondrial Ca(2)(+) signalling in adrenal glomerulosa cells.
  Journal
Pflugers Arch 464:43-50 (2012)
DOI:10.1007/s00424-012-1086-y
Reference
PMID:21962440
  Authors
Tsai LC, Beavo JA
  Title
The roles of cyclic nucleotide phosphodiesterases (PDEs) in steroidogenesis.
  Journal
Curr Opin Pharmacol 11:670-5 (2011)
DOI:10.1016/j.coph.2011.09.003
Reference
PMID:10536682
  Authors
Delcayre C, Silvestre JS
  Title
Aldosterone and the heart: towards a physiological function?
  Journal
Cardiovasc Res 43:7-12 (1999)
DOI:10.1016/S0008-6363(99)00088-7
Reference
PMID:15026188
  Authors
Lisurek M, Bernhardt R
  Title
Modulation of aldosterone and cortisol synthesis on the molecular level.
  Journal
Mol Cell Endocrinol 215:149-59 (2004)
DOI:10.1016/j.mce.2003.11.008
Reference
PMID:23628605
  Authors
Miller WL
  Title
Steroid hormone synthesis in mitochondria.
  Journal
Mol Cell Endocrinol 379:62-73 (2013)
DOI:10.1016/j.mce.2013.04.014
Reference
PMID:25788893
  Authors
Martinez-Arguelles DB, Papadopoulos V
  Title
Mechanisms mediating environmental chemical-induced endocrine disruption in the adrenal gland.
  Journal
Front Endocrinol (Lausanne) 6:29 (2015)
DOI:10.3389/fendo.2015.00029
Related
pathway
ncar00140  Steroid hormone biosynthesis
ncar00590  Arachidonic acid metabolism
ncar04020  Calcium signaling pathway
ncar04022  cGMP-PKG signaling pathway
ncar04024  cAMP signaling pathway
ncar04614  Renin-angiotensin system
ncar04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   
LinkDB

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