KEGG   PATHWAY: shr04261
Entry
shr04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Sarcophilus harrisii (Tasmanian devil)
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
shr04261  Adrenergic signaling in cardiomyocytes
shr04261

Other DBs
GO: 0001997
Organism
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
Gene
116421895  ADRB1; beta-1 adrenergic receptor [KO:K04141]
100928854  ADRB2; beta-2 adrenergic receptor [KO:K04142]
100930666  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
100922193  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100922434  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100925657  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
100920243  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100932634  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
100929278  ADCY7; adenylate cyclase type 7 isoform X3 [KO:K08047] [EC:4.6.1.1]
100923926  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
100926025  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
100933664  BVES; blood vessel epicardial substance isoform X1 [KO:K21108]
100919593  POPDC2; popeye domain-containing protein 2 isoform X1 [KO:K26206]
105750465  POPDC3; popeye domain-containing protein 3 [KO:K26207]
100935232  KCNK2; potassium channel subfamily K member 2 isoform X1 [KO:K04913]
100929360  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100915481  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100934183  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
100913731  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
100922123  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
100928210  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
100914130  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
100918637  sodium/potassium-transporting ATPase subunit alpha-2-like isoform X2 [KO:K01539] [EC:7.2.2.13]
100935132  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540]
100915285  ATP1B4; protein ATP1B4 [KO:K01540]
100915426  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
100915602  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
100929307  FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X2 [KO:K01538]
100927417  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
100932658  KCNQ1; LOW QUALITY PROTEIN: potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
100934966  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
100922398  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X3 [KO:K05850] [EC:7.2.2.10]
100921801  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
100926374  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
100930479  plasma membrane calcium-transporting ATPase 1-like [KO:K05850] [EC:7.2.2.10]
100914244  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X3 [KO:K05850] [EC:7.2.2.10]
100914566  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
100916944  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
100930572  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
100925158  sodium channel protein type 5 subunit alpha isoform X1 [KO:K04838]
100923767  SCN1B; sodium channel subunit beta-1 [KO:K04845]
100926123  SCN4B; sodium channel subunit beta-4 isoform X1 [KO:K04848]
100926503  voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
100919750  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
100927554  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
100917433  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
100929328  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
100928393  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
100925515  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
100924116  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
100915174  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X4 [KO:K04858]
100918097  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859]
100918190  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860]
100925979  voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
100934787  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
100931070  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
100923494  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
100934523  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
100913776  CACNG6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871]
116422929  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
100913513  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
100929017  CALM1; calmodulin-1 isoform X2 [KO:K02183]
100920429  CALM2; calmodulin-2 [KO:K02183]
105750699  calmodulin-A [KO:K02183]
100935134  CALM3; calmodulin-3 isoform X1 [KO:K02183]
100925046  CALML4; calmodulin-like protein 4 [KO:K02183]
116419081  calmodulin [KO:K02183]
116423459  calmodulin-like [KO:K02183]
116423460  calmodulin-like [KO:K02183]
100934917  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
100916233  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
100913975  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
100918427  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
100916914  RYR2; ryanodine receptor 2 isoform X1 [KO:K04962]
100921980  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100927043  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
100932648  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform-like [KO:K04382] [EC:3.1.3.16]
100922551  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
100927161  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100931978  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
100935274  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
100922930  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
100933266  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X3 [KO:K04354]
100916681  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
100922455  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X3 [KO:K11583]
100933047  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
100928637  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
100914332  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
100931239  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
100914865  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
100930217  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X7 [KO:K11584]
100930570  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100915116  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100920526  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
111719477  TNNC1; troponin C, slow skeletal and cardiac muscles isoform X1 [KO:K05865]
116422945  TNNI3; troponin I, cardiac muscle [KO:K12044]
100922387  TNNT2; troponin T, cardiac muscle isoform X1 [KO:K12045]
100928750  TPM1; tropomyosin alpha-1 chain isoform X6 [KO:K10373]
100933378  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
100916994  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
100932168  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
100918763  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
100925998  myosin-7 isoform X1 [KO:K17751]
100935261  MYH6; myosin-6 [KO:K17751]
100917142  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
100932686  MYL3; myosin light chain 3 [KO:K12749]
100913949  MYL4; myosin light chain 4 [KO:K12750]
100921965  PLN; cardiac phospholamban [KO:K05852]
100918964  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
105750215  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
100922099  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1 [KO:K05853] [EC:7.2.2.10]
100932795  AGT; angiotensinogen isoform X2 [KO:K09821]
100927259  AGTR1; type-1 angiotensin II receptor [KO:K04166]
100921903  AGTR2; type-2 angiotensin II receptor [KO:K04167]
100931456  ADRA1A; alpha-1A adrenergic receptor isoform X2 [KO:K04135]
100933002  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
100916183  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
100922938  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100934049  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100934311  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
100929015  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
100913337  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100923450  PPP1R1A; protein phosphatase 1 regulatory subunit 1A isoform X2 [KO:K08050]
100934330  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100913231  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100931885  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
100913327  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100914193  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X3 [KO:K04450]
100913697  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100926416  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
100913890  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
100916355  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100917654  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100923082  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
100922067  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
100932966  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
100934457  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
100934666  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100925807  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014]
100933298  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
100928729  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
100928990  MAPK11; LOW QUALITY PROTEIN: mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100925013  MAPK14; mitogen-activated protein kinase 14 isoform X2 [KO:K04441] [EC:2.7.11.24]
100925447  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100914706  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100928725  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
100916740  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
100925455  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
100931238  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
100917987  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100913262  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100925440  AKT2; RAC-beta 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
shr04020  Calcium signaling pathway
shr04151  PI3K-Akt signaling pathway
shr04260  Cardiac muscle contraction
KO pathway
ko04261   
LinkDB

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