KEGG   PATHWAY: cata04261
Entry
cata04261                   Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Cygnus atratus (black swan)
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
cata04261  Adrenergic signaling in cardiomyocytes
cata04261

Other DBs
GO: 0001997
Organism
Cygnus atratus (black swan) [GN:cata]
Gene
118248661  ADRB1; beta-1 adrenergic receptor [KO:K04141]
118254431  beta-2 adrenergic receptor isoform X1 [KO:K04142]
118248773  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
118249703  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
118251040  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
118256582  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
118243131  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
118261359  ADCY6; LOW QUALITY PROTEIN: adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
118246350  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
118252699  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
118249301  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
118257149  BVES; blood vessel epicardial substance isoform X1 [KO:K21108]
118245083  POPDC2; popeye domain-containing protein 2 isoform X1 [KO:K26206]
118257150  POPDC3; popeye domain-containing protein 3 [KO:K26207]
118255107  KCNK2; potassium channel subfamily K member 2 isoform X1 [KO:K04913]
118243752  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
118244980  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 isoform X2 [KO:K01539] [EC:7.2.2.13]
118260458  LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-2-like [KO:K01539] [EC:7.2.2.13]
118247274  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540]
118244923  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
118245462  ATP1B4; protein ATP1B4 [KO:K01540]
118252484  sodium/potassium-transporting ATPase subunit gamma-like [KO:K01538]
118255811  SLC9A1; LOW QUALITY PROTEIN: sodium/hydrogen exchanger 1 [KO:K05742]
118250065  potassium voltage-gated channel subfamily KQT member 1-like [KO:K04926]
118244327  KCNQ1; LOW QUALITY PROTEIN: potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
118247675  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
118255265  ATP2B4; plasma membrane calcium-transporting ATPase 4 [KO:K05850] [EC:7.2.2.10]
118253671  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
118250475  ATP2B1; plasma membrane calcium-transporting ATPase 1 [KO:K05850] [EC:7.2.2.10]
118244558  SLC8A3; LOW QUALITY PROTEIN: sodium/calcium exchanger 3 [KO:K05849]
118251099  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
118251891  sodium channel protein type 5 subunit alpha-like isoform X1 [KO:K04838]
118252524  SCN4B; sodium channel subunit beta-4 isoform X1 [KO:K04848]
118250054  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
118253668  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
118261499  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
118255291  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
118247429  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
118261358  CACNB3; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit beta-3 [KO:K04864]
118257760  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
118249509  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 [KO:K04858]
118248051  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
118253745  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
118250073  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
118253972  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
118250687  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
118256471  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
118253922  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
118253940  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
118259682  CALML4; calmodulin-like protein 4 [KO:K02183]
118261160  calmodulin-like [KO:K02183]
118256005  CALM2; calmodulin-2 isoform X1 [KO:K02183]
118244234  CALM1; calmodulin-1 [KO:K02183]
118258059  calmodulin, striated muscle [KO:K02183]
118247368  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
118247750  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
118260559  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
118254100  RYR2; ryanodine receptor 2 [KO:K04962]
118254959  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
118259190  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
118248342  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
118248651  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
118254907  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
118256102  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X2 [KO:K04354]
118247255  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
118253589  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
118244806  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
118250210  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
118250269  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
118252771  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
118252915  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
118256031  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
118244447  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
118257540  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
118248092  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
118255336  TNNT2; troponin T, cardiac muscle isoform X1 [KO:K12045]
118251685  TPM1; tropomyosin alpha-1 chain isoform X3 [KO:K10373]
118256686  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
118258462  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
118258736  TPM4; tropomyosin alpha-4 chain [KO:K10375]
118250760  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
118250761  actin, alpha skeletal muscle B isoform X1 [KO:K12314]
118261501  myosin-7 [KO:K17751]
118257545  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
118251806  MYL3; myosin light chain 3 isoform X1 [KO:K12749]
118258896  MYL4; myosin light chain 4 [KO:K12750]
118243876  PLN; cardiac phospholamban [KO:K05852]
118254172  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
118261520  LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 1-like [KO:K05853] [EC:7.2.2.10]
118257249  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
118243918  AGT; angiotensinogen isoform X1 [KO:K09821]
118247061  AGTR1; type-1 angiotensin II receptor [KO:K04166]
118245603  AGTR2; type-2 angiotensin II receptor [KO:K04167]
118256108  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
118256751  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
118248341  ADRA1D; alpha-1D adrenergic receptor isoform X1 [KO:K04137]
118253776  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
118244676  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
118251119  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
118251121  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858] [EC:3.1.4.11]
118253863  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
118260237  PPP1R1A; protein phosphatase 1 regulatory subunit 1A [KO:K08050]
118252877  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
118244811  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
118259031  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
118258511  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
118250509  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
118256688  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
118258774  CREB3L3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
118244746  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
118258592  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
118259195  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
118252757  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
118247475  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
118250974  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
118260218  RAPGEF3; rap guanine nucleotide exchange factor 3 [KO:K08014]
118258884  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
118254235  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
118254236  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
118255378  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
118255379  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
118259517  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
118248041  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
118249458  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
118249450  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
118255567  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
118255606  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
118261257  AKT2; LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118250209  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118256722  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [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
cata04020  Calcium signaling pathway
cata04260  Cardiac muscle contraction
KO pathway
ko04261   
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