KEGG   PATHWAY: hhv04261
Entry
hhv04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Hyaena hyaena (striped hyena)
Description
Cardiac myocytes express at least six subtypes of adrenergic receptor (AR) which include three subtypes of beta-AR (beta-1, beta-2, beta-3) and three subtypes of the alpha-1-AR (alpha-1A, alpha-1B, and alpha-1C). In the human heart the beta-1-AR is the pre- dominate receptor. Acute sympathetic stimulation of cardiac beta-1-ARs induces positive inotropic and chronotropic effects, the most effective mechanism to acutely increase output of the heart, by coupling to Gs, formation of cAMP by adenylyl cyclase (AC), and PKA- dependent phosphorylation of various target proteins (e.g., ryanodine receptor [RyR]; phospholamban [PLB], troponin I [TnI], and the L-type Ca2+ channel [LTCC]). Chronic beta-1-AR stimulation is detrimental and induces cardiomyocyte hypertrophy and apoptosis. beta-2-AR coupled to Gs exerts a proapoptotic action as well as beta-1-AR, while beta-2-AR coupled to Gi exerts an antiapoptotic action.
Class
Organismal Systems; Circulatory system
Pathway map
hhv04261  Adrenergic signaling in cardiomyocytes
hhv04261

Other DBs
GO: 0001997
Organism
Hyaena hyaena (striped hyena) [GN:hhv]
Gene
120235331  ADRB1; beta-1 adrenergic receptor [KO:K04141]
120236558  ADRB2; beta-2 adrenergic receptor [KO:K04142]
120234858  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
120234860  neuroendocrine secretory protein 55 [KO:K04632]
120238897  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
120225093  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
120235801  ADCY3; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
120247005  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
120237362  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
120223032  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
120238226  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
120221853  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
120236476  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
120247682  BVES; blood vessel epicardial substance [KO:K21108]
120242893  POPDC2; popeye domain-containing protein 2 isoform X1 [KO:K26206]
120247676  POPDC3; popeye domain-containing protein 3 [KO:K26207]
120243361  KCNK2; potassium channel subfamily K member 2 isoform X1 [KO:K04913]
120241649  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
120245321  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
120243678  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
120238762  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
120241370  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 isoform X1 [KO:K01539] [EC:7.2.2.13]
120241371  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
120238233  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
120223385  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
120231353  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
120242657  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
120230036  FXYD2; sodium/potassium-transporting ATPase subunit gamma [KO:K01538]
120231816  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
120233901  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 isoform X1 [KO:K04926]
120230080  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
120237072  ATP2B1; plasma membrane calcium-transporting ATPase 1 [KO:K05850] [EC:7.2.2.10]
120228891  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
120221711  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
120231315  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
120224258  sodium/calcium exchanger 1 isoform X1 [KO:K05849]
120225146  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
120239931  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
120235092  SCN5A; sodium channel protein type 5 subunit alpha [KO:K04838]
120243915  SCN7A; sodium channel protein type 7 subunit alpha [KO:K04839]
120226200  SCN1B; sodium channel subunit beta-1 [KO:K04845]
120229958  SCN4B; sodium channel subunit beta-4 isoform X1 [KO:K04848]
120243774  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
120239388  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
120221013  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
120228884  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
120229015  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
120240969  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
120223021  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
120225730  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 [KO:K04865]
120221165  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858]
120229292  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859]
120223632  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
120234476  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
120234176  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
120241174  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
120233279  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
120234212  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
120234221  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
120239638  CACNG6; voltage-dependent calcium channel gamma-6 subunit isoform X1 [KO:K04871]
120239747  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
120239748  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
120232098  CALM1; calmodulin-1 [KO:K02183]
120237182  calmodulin-like [KO:K02183]
120237195  calmodulin-like protein 3 [KO:K02183]
120241014  CALM2; calmodulin-2 [KO:K02183]
120221982  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
120241987  CALM3; calmodulin-3 isoform X1 [KO:K02183]
120242524  CALML6; calmodulin-like protein 6 [KO:K02183]
120233726  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
120238899  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
120222252  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
120236563  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
120246717  RYR2; ryanodine receptor 2 [KO:K04962]
120238508  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
120223033  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
120229915  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
120222367  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
120244090  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
120221673  uncharacterized protein LOC120221673 [KO:K04354]
120231861  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
120245371  PPP2R2D; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
120248361  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
120240557  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
120248228  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha [KO:K11583]
120248601  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
120238408  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
120240155  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
120230498  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
120231211  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
120244579  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
120233909  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
120239251  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
120235890  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
120239441  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
120239760  TNNI3; troponin I, cardiac muscle [KO:K12044]
120228936  TNNT2; troponin T, cardiac muscle isoform X1 [KO:K12045]
120222174  TPM1; tropomyosin alpha-1 chain isoform X1 [KO:K10373]
120221291  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
120221531  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
120239171  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
120241888  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
120247001  myosin-7 [KO:K17751]
120247013  myosin-6 [KO:K17751]
120247408  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
120229352  MYL3; myosin light chain 3 [KO:K12749]
120244252  MYL4; myosin light chain 4 isoform X1 [KO:K12750]
120241112  PLN; cardiac phospholamban [KO:K05852]
120224758  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
120239909  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
120242255  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
120237807  AGT; angiotensinogen [KO:K09821]
120237605  AGTR1; type-1 angiotensin II receptor [KO:K04166]
120239866  AGTR2; type-2 angiotensin II receptor [KO:K04167]
120244096  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
120240578  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
120226347  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
120238451  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
120232253  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
120226357  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
120226638  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
120240178  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
120234190  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
120220034  PPP1R1A; protein phosphatase 1 regulatory subunit 1A [KO:K08050]
120238830  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
120242212  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
120232080  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
120220409  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
120243894  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
120235229  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
120232978  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
120228497  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
120221289  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
120221513  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
120242085  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
120230339  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
120221927  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
120247431  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
120245032  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
120239023  RAPGEF3; rap guanine nucleotide exchange factor 3 [KO:K08014]
120236410  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
120233796  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
120233829  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
120234701  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
120235253  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
120229291  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
120244506  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
120245414  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
120241845  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
120231403  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
120231484  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
120235277  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120244696  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120247774  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
Compound
C00076  Calcium cation
C00080  H+
C00165  Diacylglycerol
C00238  Potassium cation
C00547  L-Noradrenaline
C00575  3',5'-Cyclic AMP
C00788  L-Adrenaline
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C07056  Isoproterenol
Reference
PMID:19883653
  Authors
Grimm M, Brown JH
  Title
Beta-adrenergic receptor signaling in the heart: role of CaMKII.
  Journal
J Mol Cell Cardiol 48:322-30 (2010)
DOI:10.1016/j.yjmcc.2009.10.016
Reference
PMID:21212391
  Authors
Yang JH, Saucerman JJ
  Title
Computational models reduce complexity and accelerate insight into cardiac signaling networks.
  Journal
Circ Res 108:85-97 (2011)
DOI:10.1161/CIRCRESAHA.110.223602
Reference
PMID:16765984
  Authors
Schaub MC, Hefti MA, Zaugg M
  Title
Integration of calcium with the signaling network in cardiac myocytes.
  Journal
J Mol Cell Cardiol 41:183-214 (2006)
DOI:10.1016/j.yjmcc.2006.04.005
Reference
PMID:22022314
  Authors
Taggart P, Boyett MR, Logantha S, Lambiase PD
  Title
Anger, emotion, and arrhythmias: from brain to heart.
  Journal
Front Physiol 2:67 (2011)
DOI:10.3389/fphys.2011.00067
Reference
PMID:17988210
  Authors
Bers DM
  Title
Calcium cycling and signaling in cardiac myocytes.
  Journal
Annu Rev Physiol 70:23-49 (2008)
DOI:10.1146/annurev.physiol.70.113006.100455
Reference
PMID:20923637
  Authors
Soltis AR, Saucerman JJ
  Title
Synergy between CaMKII substrates and beta-adrenergic signaling in regulation of cardiac myocyte Ca(2+) handling.
  Journal
Biophys J 99:2038-47 (2010)
DOI:10.1016/j.bpj.2010.08.016
Reference
PMID:12439640
  Authors
Wallukat G
  Title
The beta-adrenergic receptors.
  Journal
Herz 27:683-90 (2002)
DOI:10.1007/s00059-002-2434-z
Reference
PMID:11604549
  Authors
Xiao RP
  Title
Beta-adrenergic signaling in the heart: dual coupling of the beta2-adrenergic receptor to G(s) and G(i) proteins.
  Journal
Sci STKE 2001:re15 (2001)
DOI:10.1126/stke.2001.104.re15
Reference
PMID:10571541
  Authors
Xiao RP, Cheng H, Zhou YY, Kuschel M, Lakatta EG
  Title
Recent advances in cardiac beta(2)-adrenergic signal transduction.
  Journal
Circ Res 85:1092-100 (1999)
DOI:10.1161/01.RES.85.11.1092
Reference
PMID:15979723
  Authors
Zheng M, Zhu W, Han Q, Xiao RP
  Title
Emerging concepts and therapeutic implications of beta-adrenergic receptor subtype signaling.
  Journal
Pharmacol Ther 108:257-68 (2005)
DOI:10.1016/j.pharmthera.2005.04.006
Reference
PMID:17826821
  Authors
Kuzumoto M, Takeuchi A, Nakai H, Oka C, Noma A, Matsuoka S
  Title
Simulation analysis of intracellular Na+ and Cl- homeostasis during beta 1-adrenergic stimulation of cardiac myocyte.
  Journal
Prog Biophys Mol Biol 96:171-86 (2008)
DOI:10.1016/j.pbiomolbio.2007.07.005
Reference
PMID:11805843
  Authors
Bers DM
  Title
Cardiac excitation-contraction coupling.
  Journal
Nature 415:198-205 (2002)
DOI:10.1038/415198a
Reference
PMID:20658186
  Authors
Ho D, Yan L, Iwatsubo K, Vatner DE, Vatner SF
  Title
Modulation of beta-adrenergic receptor signaling in heart failure and longevity: targeting adenylyl cyclase type 5.
  Journal
Heart Fail Rev 15:495-512 (2010)
DOI:10.1007/s10741-010-9183-5
Reference
PMID:15142747
  Authors
Saucerman JJ, McCulloch AD
  Title
Mechanistic systems models of cell signaling networks: a case study of myocyte adrenergic regulation.
  Journal
Prog Biophys Mol Biol 85:261-78 (2004)
DOI:10.1016/j.pbiomolbio.2004.01.005
Reference
PMID:15765137
  Authors
Yano M, Ikeda Y, Matsuzaki M
  Title
Altered intracellular Ca2+ handling in heart failure.
  Journal
J Clin Invest 115:556-64 (2005)
DOI:10.1172/JCI24159
Reference
PMID:15232578
  Authors
Wehrens XH, Marks AR
  Title
Novel therapeutic approaches for heart failure by normalizing calcium cycling.
  Journal
Nat Rev Drug Discov 3:565-73 (2004)
DOI:10.1038/nrd1440
Reference
PMID:19874988
  Authors
Triposkiadis F, Karayannis G, Giamouzis G, Skoularigis J, Louridas G, Butler J
  Title
The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications.
  Journal
J Am Coll Cardiol 54:1747-62 (2009)
DOI:10.1016/j.jacc.2009.05.015
Reference
PMID:18407781
  Authors
Barry SP, Davidson SM, Townsend PA
  Title
Molecular regulation of cardiac hypertrophy.
  Journal
Int J Biochem Cell Biol 40:2023-39 (2008)
DOI:10.1016/j.biocel.2008.02.020
Related
pathway
hhv04020  Calcium signaling pathway
hhv04151  PI3K-Akt signaling pathway
hhv04260  Cardiac muscle contraction
KO pathway
ko04261   
LinkDB

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