KEGG   PATHWAY: zvi04261
Entry
zvi04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Zootoca vivipara (common lizard)
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
zvi04261  Adrenergic signaling in cardiomyocytes
zvi04261

Other DBs
GO: 0001997
Organism
Zootoca vivipara (common lizard) [GN:zvi]
Gene
118093408  ADRB1; beta-1 adrenergic receptor [KO:K04141]
118080289  ADRB2; beta-2 adrenergic receptor [KO:K04142]
118089017  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
118077681  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
118077623  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
118082958  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
118078718  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
118091724  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
118077506  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
118085993  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
118089989  ADCY8; LOW QUALITY PROTEIN: adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
118092905  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
118082222  BVES; blood vessel epicardial substance [KO:K21108]
118097873  POPDC2; popeye domain-containing protein 2 isoform X1 [KO:K26206]
118082223  POPDC3; popeye domain-containing protein 3 [KO:K26207]
118083173  KCNK2; potassium channel subfamily K member 2 isoform X1 [KO:K04913]
118079980  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
118088233  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
118075785  sodium/potassium-transporting ATPase subunit alpha-2 isoform X1 [KO:K01539] [EC:7.2.2.13]
118097087  sodium/potassium-transporting ATPase subunit alpha-2-like [KO:K01539] [EC:7.2.2.13]
118086200  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
118097547  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
118093584  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
118095196  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
118084350  ATP1B4; protein ATP1B4 [KO:K01540]
118084690  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
118096814  FXYD2; sodium/potassium-transporting ATPase subunit gamma [KO:K01538]
118086339  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
118087898  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 isoform X1 [KO:K04926]
118096523  potassium voltage-gated channel subfamily KQT member 1-like [KO:K04926]
118085297  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
118075200  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
118080658  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
118088146  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
118095662  plasma membrane calcium-transporting ATPase 1-like [KO:K05850] [EC:7.2.2.10]
118090657  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
118096559  plasma membrane calcium-transporting ATPase 1-like [KO:K05850] [EC:7.2.2.10]
118076375  sodium/calcium exchanger 1-like [KO:K05849]
118087205  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
118083025  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
118084088  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
118091630  LOW QUALITY PROTEIN: sodium channel protein type 5 subunit alpha-like [KO:K04838]
118092094  LOW QUALITY PROTEIN: sodium channel protein type 5 subunit alpha-like [KO:K04838]
118087926  SCN1B; sodium channel subunit beta-1 [KO:K04845]
118097301  SCN4B; sodium channel subunit beta-4 [KO:K04848]
118090932  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
118080704  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
118097569  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
118088554  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
118094447  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
118092114  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
118077483  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
118092935  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 [KO:K04865]
118090918  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858]
118080594  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
118080709  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860]
118091179  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
118079637  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
118091282  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
118092919  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
118079636  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
118079638  CACNG5; voltage-dependent calcium channel gamma-5 subunit isoform X1 [KO:K04870]
118095321  CACNG6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871]
118095909  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
118095188  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
118076518  calmodulin-1 [KO:K02183]
118077433  troponin C, skeletal muscle-like [KO:K02183]
118078175  CALM1; calmodulin-1 isoform X1 [KO:K02183]
118087100  CALM3; calmodulin-3 [KO:K02183]
118087202  CALML6; calmodulin-like protein 6 [KO:K02183]
118083088  CALM2; calmodulin-2 [KO:K02183]
118091433  calmodulin-like [KO:K02183]
118092532  CALML4; calmodulin-like protein 4 [KO:K02183]
118080422  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
118083949  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
118096405  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
118096835  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
118081853  RYR2; ryanodine receptor 2 [KO:K04962]
118097627  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
118086500  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
118080314  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
118084412  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
118096216  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
118096714  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
118093384  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
118085217  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
118076018  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
118079801  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
118080480  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
118083075  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
118083155  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
118083253  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
118090240  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
118086298  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
118080624  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
118095851  TNNI3; troponin I, cardiac muscle [KO:K12044]
118088511  TNNT2; troponin T, cardiac muscle isoform X1 [KO:K12045]
118093070  tropomyosin alpha-1 chain isoform X1 [KO:K10373]
118077101  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
118075641  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
118092467  tropomyosin alpha-1 chain-like [KO:K09290]
118085922  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
118075728  actin, alpha cardiac muscle 1-like isoform X1 [KO:K12314]
118082603  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
118085804  actin, alpha cardiac muscle 1-like [KO:K12314]
118094384  myosin-6 [KO:K17751]
118095902  myosin-7 isoform X1 [KO:K17751]
118087852  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
118092137  MYL3; myosin light chain 3 [KO:K12749]
118094626  myosin light chain 4-like [KO:K12750]
118082162  PLN; cardiac phospholamban [KO:K05852]
118078145  cardiac phospholamban [KO:K05852]
118075566  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1 [KO:K05853] [EC:7.2.2.10]
118094273  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
118096852  sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
118081902  AGT; angiotensinogen [KO:K09821]
118093608  AGTR1; type-1 angiotensin II receptor [KO:K04166]
118096907  ADRA1A; alpha-1A adrenergic receptor isoform X1 [KO:K04135]
118079070  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
118077036  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
118075670  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
118082496  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
118082497  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
118083058  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
118079639  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
118077670  PPP1R1A; protein phosphatase 1 regulatory subunit 1A [KO:K08050]
118075832  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
118094794  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
118078177  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
118096395  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
118094461  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
118090901  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
118076548  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
118077277  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
118087690  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
118090656  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
118085172  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
118092189  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
118080979  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
118091875  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
118090513  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
118077695  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014]
118094642  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
118088107  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
118088847  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
118090805  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
118091073  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
118080568  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
118088603  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
118083183  guanine nucleotide-binding protein G(i) subunit alpha-2-like [KO:K04630]
118091105  guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
118091042  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
118079928  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
118079929  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
118081845  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118079987  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118087137  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
zvi04020  Calcium signaling pathway
zvi04260  Cardiac muscle contraction
KO pathway
ko04261   
LinkDB

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