KEGG   PATHWAY: uar04925
Entry
uar04925                    Pathway                                
Name
Aldosterone synthesis and secretion - Ursus americanus (American black 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
uar04925  Aldosterone synthesis and secretion
uar04925

Other DBs
GO: 0035932
Organism
Ursus americanus (American black bear) [GN:uar]
Gene
123783095  AGT; angiotensinogen [KO:K09821]
123802390  AGTR1; type-1 angiotensin II receptor [KO:K04166]
123781527  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
123793965  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
123799710  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
123799736  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
123804253  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
123778465  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
123799165  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
123801684  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
123790908  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
123803224  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
123778823  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
123786995  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
123785895  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
123799829  PRKD3; serine/threonine-protein kinase D3 [KO:K06070] [EC:2.7.11.13]
123795721  PRKD1; serine/threonine-protein kinase D1 isoform X1 [KO:K06070] [EC:2.7.11.13]
123778726  PRKD2; serine/threonine-protein kinase D2 [KO:K06070] [EC:2.7.11.13]
123798247  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
123794100  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
123780649  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
123799579  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
123781164  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
123788905  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
123796787  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
123783374  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
123789128  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
123790975  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
123794749  ATF1; cyclic AMP-dependent transcription factor ATF-1 isoform X1 [KO:K09053]
123785121  DAGLA; diacylglycerol lipase-alpha isoform X1 [KO:K13806] [EC:3.1.1.116]
123802588  DAGLB; diacylglycerol lipase-beta [KO:K13806] [EC:3.1.1.116]
123799933  KCNK3; potassium channel subfamily K member 3 [KO:K04914]
123783193  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
123795027  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
123783365  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
123798066  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
123783612  sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
123792133  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 isoform X1 [KO:K01540]
123792376  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
123788438  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
123803404  ATP1B4; LOW QUALITY PROTEIN: protein ATP1B4 [KO:K01540]
123776816  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
123783795  CACNA1H; LOW QUALITY PROTEIN: voltage-dependent T-type calcium channel subunit alpha-1H [KO:K04855]
123780748  CACNA1I; voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856]
123777895  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
123798762  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
123797184  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
123785763  CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
123779365  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
123785908  CALM2; calmodulin-2 [KO:K02183]
123800842  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
123802291  calmodulin-like [KO:K02183]
123802321  CALML3; calmodulin-like protein 3 [KO:K02183]
123796079  CALML6; calmodulin-like protein 6 [KO:K02183]
123798898  CALM1; calmodulin-1 [KO:K02183]
123778741  CALM3; calmodulin-3 [KO:K02183]
123785810  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
123789984  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
123799188  CAMK1; calcium/calmodulin-dependent protein kinase type 1 [KO:K08794] [EC:2.7.11.17]
123793341  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
123803651  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
123789460  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
123782837  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
123779312  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
123785713  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
123780781  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
123795574  ATP2B3; LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 3 [KO:K05850] [EC:7.2.2.10]
123799209  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
123780404  LIPE; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
123777712  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
123780199  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
123799779  POMC; pro-opiomelanocortin [KO:K05228]
123803577  MC2R; adrenocorticotropic hormone receptor [KO:K04200]
123803297  neuroendocrine secretory protein 55 [KO:K04632]
123803290  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
123789481  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
123791264  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
123799951  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
123795737  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
123802178  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
123794794  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
123798393  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
123801897  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
123783548  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
123801768  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
123795272  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
123780378  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
123781928  NR4A2; nuclear receptor subfamily 4 group A member 2 [KO:K08558]
123794728  NR4A1; nuclear receptor subfamily 4 group A member 1 [KO:K04465]
123790690  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
123795008  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase [KO:K00070] [EC:1.1.1.145 5.3.3.1]
123791062  steroid 21-hydroxylase [KO:K00513] [EC:1.14.14.16]
123779108  NPPA; natriuretic peptides A [KO:K12334]
123783587  NPR1; atrial natriuretic peptide receptor 1 isoform X1 [KO:K12323] [EC:4.6.1.2]
123782529  cGMP-dependent 3',5'-cyclic phosphodiesterase [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
uar00140  Steroid hormone biosynthesis
uar00590  Arachidonic acid metabolism
uar04020  Calcium signaling pathway
uar04022  cGMP-PKG signaling pathway
uar04024  cAMP signaling pathway
uar04614  Renin-angiotensin system
uar04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   
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