KEGG   PATHWAY: teo04261
Entry
teo04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Tauraco erythrolophus (red-crested turaco)
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
teo04261  Adrenergic signaling in cardiomyocytes
teo04261

Other DBs
GO: 0001997
Organism
Tauraco erythrolophus (red-crested turaco) [GN:teo]
Gene
104382737  ADRB2; beta-2 adrenergic receptor [KO:K04142]
104384533  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
104371857  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
104381100  ADCY3; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
104371518  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
104376345  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
104373465  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
104381564  BVES; LOW QUALITY PROTEIN: blood vessel epicardial substance [KO:K21108]
104377484  POPDC2; popeye domain-containing protein 2 isoform X1 [KO:K26206]
104372679  POPDC3; popeye domain-containing protein 3 [KO:K26207]
104376330  KCNK2; potassium channel subfamily K member 2 [KO:K04913]
104370618  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
104384027  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
104372833  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
104373060  ATP1B4; protein ATP1B4 [KO:K01540]
104378751  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
104376294  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
104377145  LOW QUALITY PROTEIN: potassium voltage-gated channel subfamily KQT member 1-like [KO:K04926]
104384326  potassium voltage-gated channel subfamily KQT member 1-like [KO:K04926]
104369601  potassium voltage-gated channel subfamily E member 1-like [KO:K04894]
104380697  plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
104378165  LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 1-like [KO:K05850] [EC:7.2.2.10]
104379331  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
104372067  sodium/calcium exchanger 3 [KO:K05849]
104372204  SLC8A1; sodium/calcium exchanger 1 [KO:K05849]
104380089  sodium channel protein type 5 subunit alpha-like isoform X1 [KO:K04838]
104375737  SCN4B; sodium channel subunit beta-4 [KO:K04848]
104379566  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
104380113  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
104383219  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 [KO:K04863]
104374666  voltage-dependent L-type calcium channel subunit beta-4 [KO:K04865]
104379136  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 [KO:K04858]
104376050  voltage-dependent calcium channel subunit alpha-2/delta-3-like [KO:K04860]
104378050  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
104375407  CACNG2; LOW QUALITY PROTEIN: voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
104384118  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
104378051  CACNG4; LOW QUALITY PROTEIN: voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
104372839  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
104380321  calmodulin-A-like [KO:K02183]
104378169  LOW QUALITY PROTEIN: calmodulin-A-like [KO:K02183]
104373761  CALML4; calmodulin-like protein 4 [KO:K02183]
104381196  calcium/calmodulin-dependent protein kinase type II subunit gamma-like [KO:K04515] [EC:2.7.11.17]
104379757  calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
104382102  RYR2; ryanodine receptor 2 [KO:K04962]
104371019  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
104373268  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform-like [KO:K04382] [EC:3.1.3.16]
104380619  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform isoform X1 [KO:K04354]
104384028  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
104379079  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
104370119  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
104376978  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
104383632  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
104370403  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
104372908  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
104373266  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
104379346  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]
104375071  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
104383617  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
104370032  serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
104371070  TNNC1; troponin C, slow skeletal and cardiac muscles isoform X1 [KO:K05865]
104377064  TNNT2; LOW QUALITY PROTEIN: troponin T, cardiac muscle [KO:K12045]
104371060  tropomyosin alpha-3 chain-like isoform X1 [KO:K10373]
104378344  tropomyosin alpha-3 chain isoform X1 [KO:K09290]
104370338  tropomyosin alpha-1 chain-like [KO:K10375]
104370627  actin, gamma-enteric smooth muscle-like [KO:K12314]
104370607  actin, alpha cardiac muscle 1 [KO:K12314]
104383163  LOW QUALITY PROTEIN: myosin-6-like [KO:K17751]
104375552  myosin regulatory light chain 2A, cardiac muscle isoform-like [KO:K10351]
104375943  myosin regulatory light chain 2A, cardiac muscle isoform [KO:K10351]
104373238  MYL3; myosin light chain 3 [KO:K12749]
104381160  MYL4; myosin light chain 4 [KO:K12750]
104377751  PLN; cardiac phospholamban [KO:K05852]
104375551  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
104379228  AGT; angiotensinogen [KO:K09821]
104373078  AGTR1; type-1 angiotensin II receptor [KO:K04166]
104374859  AGTR2; type-2 angiotensin II receptor [KO:K04167]
104382418  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
104381888  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
104372259  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
104376224  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
104378121  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
104373337  LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
104375480  protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
104379055  LOW QUALITY PROTEIN: mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
104383641  RPS6KA5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:2.7.11.1]
104380683  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
104372757  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
104375020  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
104371775  LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
104377848  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
104373312  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
104373930  cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
104372767  LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 5-like [KO:K09047]
104371407  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
104384091  apoptosis regulator Bcl-2-like [KO:K02161]
104381085  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
104377471  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
104371460  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
104379224  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
104380786  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
104375801  guanine nucleotide-binding protein G(k) subunit alpha-like [KO:K04630]
104374189  guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
104379622  guanine nucleotide-binding protein G(k) subunit alpha-like [KO:K04630]
104369617  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
104373151  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
104384693  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
104380196  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104374433  AKT1; RAC-alpha 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
teo04020  Calcium signaling pathway
teo04260  Cardiac muscle contraction
KO pathway
ko04261   
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