KEGG   PATHWAY: scan04261
Entry
scan04261                   Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Serinus canaria (common canary)
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
scan04261  Adrenergic signaling in cardiomyocytes
scan04261

Other DBs
GO: 0001997
Organism
Serinus canaria (common canary) [GN:scan]
Gene
103814126  ADRB1; beta-1 adrenergic receptor [KO:K04141]
103817524  ADRB2; beta-2 adrenergic receptor [KO:K04142]
103818880  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
103819377  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
103815408  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
103814312  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
103824610  ADCY6; LOW QUALITY PROTEIN: adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
103816806  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
103816719  ADCY8; adenylate cyclase type 8 isoform X2 [KO:K08048] [EC:4.6.1.1]
103817765  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
103818873  BVES; blood vessel epicardial substance isoform X1 [KO:K21108]
103827113  POPDC2; popeye domain-containing protein 2 isoform X2 [KO:K26206]
103818862  POPDC3; popeye domain-containing protein 3 [KO:K26207]
103821508  KCNK2; potassium channel subfamily K member 2 [KO:K04913]
103814927  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
103827109  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
103815419  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
103812425  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 isoform X1 [KO:K01540]
103816394  ATP1B4; protein ATP1B4 isoform X2 [KO:K01540]
108963268  FXYD2; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit gamma [KO:K01538]
103823594  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
103827015  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
103819716  potassium voltage-gated channel subfamily KQT member 1-like [KO:K04926]
103815737  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
103824510  ATP2B4; LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 4 [KO:K05850] [EC:7.2.2.10]
103813406  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
103816942  ATP2B2; plasma membrane calcium-transporting ATPase 2 [KO:K05850] [EC:7.2.2.10]
103826617  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
103825387  sodium/calcium exchanger 2-like [KO:K05849]
103821334  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
103813057  sodium channel protein type 5 subunit alpha-like [KO:K04838]
103812707  sodium channel protein type 5 subunit alpha-like isoform X1 [KO:K04838]
115484269  sodium channel subunit beta-1-like [KO:K04845]
103823018  SCN4B; sodium channel subunit beta-4 isoform X3 [KO:K04848]
103820462  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
103816992  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
103822432  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
103812781  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X4 [KO:K04863]
103814617  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X2 [KO:K04865]
103813738  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858]
103817134  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
103816995  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
103820520  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
103819769  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
103813220  CACNG2; voltage-dependent calcium channel gamma-2 subunit isoform X1 [KO:K04867]
103817800  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
103819766  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
103819768  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
103825329  voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
103817225  CALM2; calmodulin-2 [KO:K02183]
103816252  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
103822470  calmodulin, striated muscle [KO:K02183]
103826480  CALM1; calmodulin-1 [KO:K02183]
103817304  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
103822722  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
103815714  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
103813998  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
103818574  RYR2; ryanodine receptor 2 [KO:K04962]
103817471  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
103823422  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
103817406  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
103824110  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X2 [KO:K04354]
103822705  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
103814089  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
103812324  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
103815474  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha [KO:K11583]
103826933  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
103821519  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
103826366  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X2 [KO:K11584]
103826422  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
103821293  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
115484937  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform-like [KO:K11584]
103817249  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
103818147  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
103822255  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
103816983  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
103822364  TNNT2; troponin T, cardiac muscle isoform X1 [KO:K12045]
103815954  TPM1; tropomyosin alpha-1 chain isoform X2 [KO:K10373]
103823969  TPM3; tropomyosin alpha-3 chain isoform X9 [KO:K09290]
103824118  TPM4; tropomyosin alpha-4 chain isoform X2 [KO:K10375]
103822891  TPM2; tropomyosin beta chain isoform X1 [KO:K10375]
103826575  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
103825210  LOW QUALITY PROTEIN: myosin-6-like [KO:K17751]
103815441  LOW QUALITY PROTEIN: myosin-6-like [KO:K17751]
103815434  LOW QUALITY PROTEIN: myosin-7-like [KO:K17751]
103818146  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
103812673  MYL3; myosin light chain 3 [KO:K12749]
103821661  MYL4; myosin light chain 4 [KO:K12750]
103818356  PLN; cardiac phospholamban [KO:K05852]
103818170  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
103820058  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
103818499  AGT; angiotensinogen isoform X3 [KO:K09821]
103815406  AGTR1; type-1 angiotensin II receptor [KO:K04166]
103816409  AGTR2; type-2 angiotensin II receptor [KO:K04167]
103822708  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
103817536  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
103823103  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
103823251  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
103824735  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
103822183  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
103819233  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
103819309  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
103819765  PRKCA; protein kinase C alpha type isoform X3 [KO:K02677] [EC:2.7.11.13]
103818074  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103826478  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
103814492  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
103814449  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
103813275  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
103819702  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
103824532  CREB3L3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
103826679  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
103822893  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
103825377  cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
115484624  CREB3L4; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
103812908  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X5 [KO:K09047]
103812742  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
108964924  BCL2; apoptosis regulator Bcl-2 isoform X2 [KO:K02161]
115483875  LOW QUALITY PROTEIN: rap guanine nucleotide exchange factor 3-like [KO:K08014]
103814439  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
103813699  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
103823281  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
103823282  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103813488  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103813540  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
103824284  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
103822350  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
103813517  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
103820021  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
103820022  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
103817751  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103826388  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
scan04020  Calcium signaling pathway
scan04260  Cardiac muscle contraction
KO pathway
ko04261   
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