KEGG   PATHWAY: caty04925
Entry
caty04925                   Pathway                                
Name
Aldosterone synthesis and secretion - Cercocebus atys (sooty mangabey)
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
caty04925  Aldosterone synthesis and secretion
caty04925

Other DBs
GO: 0035932
Organism
Cercocebus atys (sooty mangabey) [GN:caty]
Gene
105574840  AGT; angiotensinogen [KO:K09821]
105587504  AGTR1; type-1 angiotensin II receptor isoform X1 [KO:K04166]
105584209  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
105591769  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
105577494  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
105574260  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105582089  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105582092  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105585726  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105601409  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
105593244  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
105599331  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
105586076  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
105595654  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
105590592  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
105592265  PRKD1; serine/threonine-protein kinase D1 isoform X1 [KO:K06070] [EC:2.7.11.13]
105595189  PRKD2; serine/threonine-protein kinase D2 [KO:K06070] [EC:2.7.11.13]
105597181  PRKD3; serine/threonine-protein kinase D3 isoform X1 [KO:K06070] [EC:2.7.11.13]
105580103  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105579833  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
105572871  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105592792  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
105593478  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
105589639  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105598130  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105591802  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
105595971  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
105574100  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
105580351  ATF1; cyclic AMP-dependent transcription factor ATF-1 isoform X1 [KO:K09053]
105577585  DAGLA; sn1-specific diacylglycerol lipase alpha isoform X1 [KO:K13806] [EC:3.1.1.116]
105584357  DAGLB; sn1-specific diacylglycerol lipase beta isoform X1 [KO:K13806] [EC:3.1.1.116]
105578494  KCNK3; potassium channel subfamily K member 3 [KO:K04914]
105581151  KCNK9; potassium channel subfamily K member 9 [KO:K04919]
105582639  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
105589285  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 isoform X1 [KO:K01539] [EC:7.2.2.13]
105589286  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 isoform X1 [KO:K01539] [EC:7.2.2.13]
105596327  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 isoform X1 [KO:K01539] [EC:7.2.2.13]
105598041  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
105600169  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
105586350  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540]
105582250  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
105598361  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
105579425  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
105574047  CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H isoform X1 [KO:K04855]
105572851  CACNA1I; voltage-dependent T-type calcium channel subunit alpha-1I isoform X1 [KO:K04856]
105582968  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
105585586  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
105573107  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
105575216  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
105590966  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
105600970  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
105594435  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
105595186  CALM3; calmodulin isoform X1 [KO:K02183]
105596563  CALM1; calmodulin [KO:K02183]
105581752  calmodulin-like [KO:K02183]
105597438  CALML3; calmodulin-like protein 3 [KO:K02183]
105597439  CALML5; calmodulin-like protein 5 [KO:K02183]
105590605  CALM2; calmodulin [KO:K02183]
105577074  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
105585762  CAMK1; calcium/calmodulin-dependent protein kinase type 1 isoform X1 [KO:K08794] [EC:2.7.11.17]
105573807  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
105571464  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
105596908  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
105589879  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
105597344  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
105576638  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
105585782  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
105596823  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
105574405  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
105598747  LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 3-like [KO:K05850] [EC:7.2.2.10]
105575889  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
105598066  LIPE; hormone-sensitive lipase [KO:K07188] [EC:3.1.1.79]
105571287  LDLR; low-density lipoprotein receptor [KO:K12473]
105591023  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
105578520  POMC; pro-opiomelanocortin [KO:K05228]
105598919  MC2R; adrenocorticotropic hormone receptor [KO:K04200]
105585318  neuroendocrine secretory protein 55 [KO:K04632]
105585319  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
105588320  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
105585972  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
105578529  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
105600225  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
105589787  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
105580404  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
105588901  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105588369  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
105572097  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
105593561  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105601580  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
105584148  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
105581294  cytochrome P450 11B2, mitochondrial-like [KO:K07433] [EC:1.14.15.4 1.14.15.5]
105590792  STAR; steroidogenic acute regulatory protein, mitochondrial isoform X1 [KO:K16931]
105576001  NR4A2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
105580323  NR4A1; nuclear receptor subfamily 4 group A member 1 isoform X1 [KO:K04465]
105600069  cholesterol side-chain cleavage enzyme, mitochondrial isoform X1 [KO:K00498] [EC:1.14.15.6]
105599590  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
105599597  HSD3B2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
105574106  LOW QUALITY PROTEIN: steroid 21-hydroxylase [KO:K00513] [EC:1.14.14.16]
105580855  NPPA; natriuretic peptides A [KO:K12334]
105593468  NPR1; atrial natriuretic peptide receptor 1 isoform X1 [KO:K12323] [EC:4.6.1.2]
105578787  PDE2A; 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
caty00140  Steroid hormone biosynthesis
caty00590  Arachidonic acid metabolism
caty04020  Calcium signaling pathway
caty04022  cGMP-PKG signaling pathway
caty04024  cAMP signaling pathway
caty04614  Renin-angiotensin system
caty04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   
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