KEGG   PATHWAY: ppam04925
Entry
ppam04925                   Pathway                                
Name
Aldosterone synthesis and secretion - Pteronotus mesoamericanus (Parnell's mustached bat)
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
ppam04925  Aldosterone synthesis and secretion
ppam04925

Other DBs
GO: 0035932
Organism
Pteronotus mesoamericanus (Parnell's mustached bat) [GN:ppam]
Gene
129073055  AGT; angiotensinogen [KO:K09821]
129079912  AGTR1; type-1 angiotensin II receptor [KO:K04166]
129078244  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
129074308  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
129068613  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
129064066  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
129070855  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
129070857  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
129087685  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
129084965  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
129067386  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
129070225  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
129076731  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
129081586  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
129065757  PRKCE; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
129082876  PRKD2; serine/threonine-protein kinase D2 [KO:K06070] [EC:2.7.11.13]
129066203  PRKD3; serine/threonine-protein kinase D3 [KO:K06070] [EC:2.7.11.13]
129074178  PRKD1; serine/threonine-protein kinase D1 isoform X1 [KO:K06070] [EC:2.7.11.13]
129080390  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
129061773  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
129077836  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
129081516  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
129062388  CREB3L4; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
129062851  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
129078156  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
129079431  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
129063111  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
129067339  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
129084850  ATF1; cyclic AMP-dependent transcription factor ATF-1 isoform X1 [KO:K09053]
129062756  DAGLA; diacylglycerol lipase-alpha [KO:K13806] [EC:3.1.1.116]
129067999  DAGLB; diacylglycerol lipase-beta [KO:K13806] [EC:3.1.1.116]
129067121  KCNK3; potassium channel subfamily K member 3 [KO:K04914]
129084090  KCNK9; potassium channel subfamily K member 9 [KO:K04919]
129075344  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
129062260  sodium/potassium-transporting ATPase subunit alpha-2 isoform X1 [KO:K01539] [EC:7.2.2.13]
129062319  sodium/potassium-transporting ATPase subunit alpha-4 isoform X1 [KO:K01539] [EC:7.2.2.13]
129075409  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
129063843  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
129082056  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
129065423  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
129072291  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
129087864  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
129080142  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
129083353  CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H isoform X1 [KO:K04855]
129077935  CACNA1I; voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856]
129073529  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
129088299  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
129065030  CACNA1F; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
129072943  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
129087147  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
129063259  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
129082875  CALM3; calmodulin-3 [KO:K02183]
129084580  calmodulin-like [KO:K02183]
129065634  CALM2; calmodulin-2 [KO:K02183]
129065835  CALM1; calmodulin-1 [KO:K02183]
129078752  CALML6; calmodulin-like protein 6 [KO:K02183]
129086576  calmodulin-alpha-like [KO:K02183]
129087301  CALML3; calmodulin-like protein 3 [KO:K02183]
129062408  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
129086851  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
129087831  CAMK1; calcium/calmodulin-dependent protein kinase type 1 isoform X1 [KO:K08794] [EC:2.7.11.17]
129062638  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
129068934  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
129069869  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
129066548  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
129083913  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
129062310  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
129075941  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
129074353  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
129088193  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
129066147  LIPE; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
129061362  LDLR; low-density lipoprotein receptor [KO:K12473]
129087161  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
129065100  POMC; pro-opiomelanocortin [KO:K05228]
129081756  MC2R; adrenocorticotropic hormone receptor [KO:K04200]
129070595  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
129070597  neuroendocrine secretory protein 55-like [KO:K04632]
129068928  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
129074539  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
129067273  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
129074168  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
129071827  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
129084881  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
129068161  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
129084082  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
129083643  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
129061554  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
129065641  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
129064814  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
129061637  NR4A2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
129084834  NR4A1; nuclear receptor subfamily 4 group A member 1 [KO:K04465]
129079756  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
129063973  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
129067338  steroid 21-hydroxylase [KO:K00513] [EC:1.14.14.16]
129075595  NPPA; natriuretic peptides A [KO:K12334]
129062087  NPR1; atrial natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
129072725  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
ppam00140  Steroid hormone biosynthesis
ppam00590  Arachidonic acid metabolism
ppam04020  Calcium signaling pathway
ppam04022  cGMP-PKG signaling pathway
ppam04024  cAMP signaling pathway
ppam04614  Renin-angiotensin system
ppam04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   
LinkDB

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