KEGG   PATHWAY: umr04925
Entry
umr04925                    Pathway                                
Name
Aldosterone synthesis and secretion - Ursus maritimus (polar bear)
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
umr04925  Aldosterone synthesis and secretion
umr04925

Other DBs
GO: 0035932
Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103656752  KCNK9; potassium channel subfamily K member 9 [KO:K04919]
103657204  CALM3; calmodulin-3 [KO:K02183]
103657206  PRKD2; serine/threonine-protein kinase D2 isoform X1 [KO:K06070] [EC:2.7.11.13]
103657738  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
103657769  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
103658932  [KO:K09047]
103659124  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
103659593  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
103659802  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
103659857  NR4A2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
103660077  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
103660367  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
103660668  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
103660890  CACNA1G; LOW QUALITY PROTEIN: voltage-dependent T-type calcium channel subunit alpha-1G [KO:K04854]
103661123  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
103661271  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
103661704  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
103661761  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X3 [KO:K04515] [EC:2.7.11.17]
103661870  AGT; angiotensinogen [KO:K09821]
103662972  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
103663281  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
103664598  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
103665275  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103665553  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103665907  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
103666859  NPPA; natriuretic peptides A [KO:K12334]
103667087  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
103667625  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
103668027  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
103668409  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
103668547  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
103668723  NPR1; atrial natriuretic peptide receptor 1 isoform X1 [KO:K12323] [EC:4.6.1.2]
103668755  CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H isoform X1 [KO:K04855]
103668895  PRKCB; LOW QUALITY PROTEIN: protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
103669052  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
103669178  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
103669413  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
103669556  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
103669575  CAMK1; calcium/calmodulin-dependent protein kinase type 1 isoform X1 [KO:K08794] [EC:2.7.11.17]
103669597  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103670093  DAGLB; diacylglycerol lipase-beta [KO:K13806] [EC:3.1.1.116]
103670304  CALM1; calmodulin-1 isoform X1 [KO:K02183]
103670935  [KO:K04632]
103670936  [KO:K04632]
103671225  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
103671240  CALM2; calmodulin-2 [KO:K02183]
103671574  PRKD3; serine/threonine-protein kinase D3 isoform X1 [KO:K06070] [EC:2.7.11.13]
103671685  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
103671921  KCNK3; potassium channel subfamily K member 3 [KO:K04914]
103672049  [KO:K01539] [EC:7.2.2.13]
103672113  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
103672393  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
103672536  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
103672914  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
103673552  [KO:K05858] [EC:3.1.4.11]
103673916  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
103674425  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
103674426  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
103674675  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
103674683  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
103674739  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
103675480  ATF1; cyclic AMP-dependent transcription factor ATF-1 isoform X1 [KO:K09053]
103675500  NR4A1; nuclear receptor subfamily 4 group A member 1 [KO:K04465]
103675618  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
103675706  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
103675811  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
103676238  [KO:K02183]
103676239  CALML3; calmodulin-like protein 3 [KO:K02183]
103676294  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D [KO:K08794] [EC:2.7.11.17]
103676370  CACNA1I; voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856]
103676372  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
103677123  [KO:K00070] [EC:1.1.1.145 5.3.3.1]
103678109  PDE2A; cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X1 [KO:K18283] [EC:3.1.4.17]
103678133  AGTR1; type-1 angiotensin II receptor [KO:K04166]
103678227  DAGLA; diacylglycerol lipase-alpha [KO:K13806] [EC:3.1.1.116]
103678432  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540]
103678713  LDLR; low-density lipoprotein receptor [KO:K12473]
103678826  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
103678997  [KO:K00498] [EC:1.14.15.6]
103679049  CALML4; calmodulin-like protein 4 isoform X3 [KO:K02183]
103679250  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
103679331  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
103679549  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
103679703  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
103680155  LIPE; hormone-sensitive lipase [KO:K07188] [EC:3.1.1.79]
103680185  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
103680217  ATP1B4; protein ATP1B4 [KO:K01540]
103680476  MC2R; adrenocorticotropic hormone receptor [KO:K04200]
103680885  PRKD1; LOW QUALITY PROTEIN: serine/threonine-protein kinase D1 [KO:K06070] [EC:2.7.11.13]
103681679  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
103681813  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
103682041  CALML6; calmodulin-like protein 6 [KO:K02183]
103682183  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103682282  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
103682334  [KO:K00513] [EC:1.14.14.16]
121099746  [KO:K05858] [EC:3.1.4.11]
121101079  POMC; pro-opiomelanocortin [KO:K05228]
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
umr00140  Steroid hormone biosynthesis
umr00590  Arachidonic acid metabolism
umr04020  Calcium signaling pathway
umr04022  cGMP-PKG signaling pathway
umr04024  cAMP signaling pathway
umr04614  Renin-angiotensin system
umr04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   

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