KEGG   PATHWAY: bbub04925
Entry
bbub04925                   Pathway                                
Name
Aldosterone synthesis and secretion - Bubalus bubalis (water buffalo)
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
bbub04925  Aldosterone synthesis and secretion
bbub04925

Other DBs
GO: 0035932
Organism
Bubalus bubalis (water buffalo) [GN:bbub]
Gene
102389327  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
102389415  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X19 [KO:K04515] [EC:2.7.11.17]
102389539  PRKD3; serine/threonine-protein kinase D3 [KO:K06070] [EC:2.7.11.13]
102389675  LIPE; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
102389738  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
102389945  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
102390342  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X4 [KO:K05850] [EC:7.2.2.10]
102391004  LDLR; low-density lipoprotein receptor [KO:K12473]
102391404  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
102391725  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
102391819  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
102392060  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
102392366  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
102392963  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X3 [KO:K09049]
102393025  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
102393344  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102393421  [KO:K02183]
102393496  NR4A1; nuclear receptor subfamily 4 group A member 1 isoform X1 [KO:K04465]
102393547  CAMK1; calcium/calmodulin-dependent protein kinase type 1 isoform X1 [KO:K08794] [EC:2.7.11.17]
102394074  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
102394885  [KO:K00513] [EC:1.14.14.16]
102395032  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
102395043  KCNK3; potassium channel subfamily K member 3 [KO:K04914]
102395302  ADCY8; adenylate cyclase type 8 isoform X3 [KO:K08048] [EC:4.6.1.1]
102395917  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X2 [KO:K05850] [EC:7.2.2.10]
102396037  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
102396094  CALM1; calmodulin-1 isoform X2 [KO:K02183]
102396837  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X2 [KO:K04854]
102396896  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
102397191  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
102397328  PRKD1; serine/threonine-protein kinase D1 isoform X1 [KO:K06070] [EC:2.7.11.13]
102397549  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
102397646  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
102398301  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X2 [KO:K09048]
102398422  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
102400151  [KO:K00498] [EC:1.14.15.6]
102400784  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
102400838  ATF1; cyclic AMP-dependent transcription factor ATF-1 isoform X1 [KO:K09053]
102400864  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X4 [KO:K09047]
102401062  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
102401420  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
102401906  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
102402620  PDE2A; cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X1 [KO:K18283] [EC:3.1.4.17]
102403292  [KO:K02183]
102403583  DAGLA; diacylglycerol lipase-alpha [KO:K13806] [EC:3.1.1.116]
102403925  NR4A2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
102404282  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
102404308  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
102404548  DAGLB; diacylglycerol lipase-beta isoform X3 [KO:K13806] [EC:3.1.1.116]
102404606  PRKCE; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
102405249  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
102405290  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
102405387  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
102405550  PRKD2; serine/threonine-protein kinase D2 isoform X1 [KO:K06070] [EC:2.7.11.13]
102405655  [KO:K02183]
102405830  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
102405960  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 isoform X2 [KO:K01539] [EC:7.2.2.13]
102406078  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
102406525  CALM3; calmodulin-3 [KO:K02183]
102406795  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X3 [KO:K05850] [EC:7.2.2.10]
102406935  AGTR1; type-1 angiotensin II receptor [KO:K04166]
102407189  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
102407190  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X9 [KO:K04850]
102407250  KCNK9; potassium channel subfamily K member 9 [KO:K04919]
102407343  NPR1; atrial natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
102407399  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
102407637  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
102407976  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
102408103  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
102408582  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
102408597  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
102408739  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G isoform X1 [KO:K08794] [EC:2.7.11.17]
102409250  [KO:K04634]
102409793  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
102410016  SCARB1; scavenger receptor class B member 1 isoform X2 [KO:K13885]
102410456  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
102410577  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
102410708  POMC; pro-opiomelanocortin [KO:K05228]
102410810  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
102410813  CALM2; calmodulin-2 [KO:K02183]
102412320  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
102412452  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X8 [KO:K04958]
102412622  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
102413383  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X4 [KO:K04345] [EC:2.7.11.11]
102413429  [KO:K00070] [EC:1.1.1.145 5.3.3.1]
102413748  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
102415323  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
102415383  AGT; angiotensinogen [KO:K09821]
102415611  PRKCA; protein kinase C alpha type isoform X4 [KO:K02677] [EC:2.7.11.13]
102415635  MC2R; adrenocorticotropic hormone receptor [KO:K04200]
102415705  CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H isoform X4 [KO:K04855]
102415997  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X3 [KO:K08794] [EC:2.7.11.17]
102416387  [KO:K02183]
102416446  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X7 [KO:K04515] [EC:2.7.11.17]
102416630  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
112577614  [KO:K04632]
112580290  [KO:K04374]
123465754  NPPA; natriuretic peptides A [KO:K12334]
123466194  [KO:K02183]
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
bbub00140  Steroid hormone biosynthesis
bbub00590  Arachidonic acid metabolism
bbub04020  Calcium signaling pathway
bbub04022  cGMP-PKG signaling pathway
bbub04024  cAMP signaling pathway
bbub04614  Renin-angiotensin system
bbub04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   

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