KEGG   PATHWAY: myb04261
Entry
myb04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Myotis brandtii (Brandt's bat)
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
myb04261  Adrenergic signaling in cardiomyocytes
myb04261

Other DBs
GO: 0001997
Organism
Myotis brandtii (Brandt's bat) [GN:myb]
Gene
102258046  ADRB1; adrenoceptor beta 1 [KO:K04141]
102249639  ADRB2; adrenoceptor beta 2 [KO:K04142]
102252262  guanine nucleotide-binding protein G(s) subunit alpha isoforms short [KO:K04632]
102255448  neuroendocrine secretory protein 55 [KO:K04632]
102257679  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
102260356  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
102261014  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
102247996  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
102257731  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102248773  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102253549  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102249345  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102248953  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102261456  BVES; blood vessel epicardial substance [KO:K21108]
102247392  POPDC2; popeye domain containing 2 [KO:K26206]
102261167  POPDC3; popeye domain containing 3 [KO:K26207]
102263619  potassium channel subfamily K member 2 [KO:K04913]
102244919  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
102252927  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102243691  ATP1A1; ATPase Na+/K+ transporting subunit alpha 1 [KO:K01539] [EC:7.2.2.13]
102243972  ATP1A4; ATPase Na+/K+ transporting subunit alpha 4 [KO:K01539] [EC:7.2.2.13]
102244267  ATP1A2; ATPase Na+/K+ transporting subunit alpha 2 [KO:K01539] [EC:7.2.2.13]
102242637  ATP1A3; ATPase Na+/K+ transporting subunit alpha 3 [KO:K01539] [EC:7.2.2.13]
102243046  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
102244043  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
102245478  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
102260344  SLC9A1; solute carrier family 9 member A1 [KO:K05742]
102246906  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
102254169  plasma membrane calcium-transporting ATPase 4 [KO:K05850] [EC:7.2.2.10]
102239691  ATP2B3; ATPase plasma membrane Ca2+ transporting 3 [KO:K05850] [EC:7.2.2.10]
102259512  ATP2B2; ATPase plasma membrane Ca2+ transporting 2 [KO:K05850] [EC:7.2.2.10]
102259346  ATP2B4; ATPase plasma membrane Ca2+ transporting 4 [KO:K05850] [EC:7.2.2.10]
102257503  ATP2B1; ATPase plasma membrane Ca2+ transporting 1 [KO:K05850] [EC:7.2.2.10]
102254673  SLC8A1; solute carrier family 8 member A1 [KO:K05849]
102242099  SLC8A3; solute carrier family 8 member A3 [KO:K05849]
102240070  SCN5A; sodium voltage-gated channel alpha subunit 5 [KO:K04838]
102249369  SCN7A; sodium voltage-gated channel alpha subunit 7 [KO:K04839]
102262662  SCN1B; sodium voltage-gated channel beta subunit 1 [KO:K04845]
102242089  SCN4B; sodium voltage-gated channel beta subunit 4 [KO:K04848]
102240225  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
102259218  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
102260789  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
102243265  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
102247800  CACNB1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04862]
102243843  CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863]
102247877  CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864]
102261332  CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865]
102238945  CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858]
102239809  CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859]
102239827  voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
102254288  CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861]
102259942  CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866]
102244899  CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867]
102240803  CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868]
102244082  CACNG4; calcium voltage-gated channel auxiliary subunit gamma 4 [KO:K04869]
102260251  CACNG5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870]
102252645  CACNG6; calcium voltage-gated channel auxiliary subunit gamma 6 [KO:K04871]
102249601  CACNG7; calcium voltage-gated channel auxiliary subunit gamma 7 [KO:K04872]
102260757  CACNG8; calcium voltage-gated channel auxiliary subunit gamma 8 [KO:K04873]
102244216  CALM2; calmodulin 2 [KO:K02183]
102251233  CALM1; calmodulin 1 [KO:K02183]
102253504  CALML3; calmodulin-like protein 3 [KO:K02183]
102253811  CALML5; calmodulin like 5 [KO:K02183]
102240022  CALML6; calmodulin like 6 [KO:K02183]
102251350  CALM3; calmodulin 3 [KO:K02183]
102256865  calmodulin [KO:K02183]
102242522  CALML4; calmodulin like 4 [KO:K02183]
102252254  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
102262365  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
102260966  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
102257317  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
102263572  RYR2; ryanodine receptor 2 [KO:K04962]
102246010  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
102255371  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
102262643  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
102254517  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
102243537  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
102240425  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
102238990  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
102254637  PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
102248512  PPP2R3C; protein phosphatase 2 regulatory subunit B''gamma [KO:K11583]
106725200  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta-like [KO:K11583]
102240816  PPP2R3A; protein phosphatase 2 regulatory subunit B''alpha [KO:K11583]
102241218  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
102242374  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
102239026  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
102249194  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
102244211  PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
102244214  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
102253559  serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
102248545  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
102239740  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
102247142  TNNC1; troponin C1, slow skeletal and cardiac type [KO:K05865]
102263101  TNNT2; troponin T2, cardiac type [KO:K12045]
102250595  TPM1; tropomyosin 1 (alpha) [KO:K10373]
102242850  TPM2; tropomyosin 2 (beta) [KO:K10374]
102259211  TPM3; tropomyosin 3 [KO:K09290]
102250863  TPM4; tropomyosin 4 [KO:K10375]
102247353  ACTC1; actin, alpha, cardiac muscle 1 [KO:K12314]
102250088  MYH6; myosin-6 [KO:K17751]
102249796  MYH7; myosin-7 [KO:K17751]
102258260  MYL2; myosin light chain 2 [KO:K10351]
102258821  MYL3; myosin light chain 3 [KO:K12749]
102262432  MYL4; myosin light chain 4 [KO:K12750]
102247697  PLN; phospholamban [KO:K05852]
102242162  ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:7.2.2.10]
102239308  ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853] [EC:7.2.2.10]
102263136  ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:7.2.2.10]
102262829  AGT; angiotensinogen [KO:K09821]
102245101  AGTR1; angiotensin II receptor type 1 [KO:K04166]
102260858  AGTR2; angiotensin II receptor type 2 [KO:K04167]
102249717  ADRA1A; adrenoceptor alpha 1A [KO:K04135]
102248047  ADRA1B; adrenoceptor alpha 1B [KO:K04136]
102243958  ADRA1D; adrenoceptor alpha 1D [KO:K04137]
102247263  GNAQ; G protein subunit alpha q [KO:K04634]
102238655  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102254054  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102241255  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102240650  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102260557  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102238678  PPP1R1A; protein phosphatase 1 regulatory inhibitor subunit 1A [KO:K08050]
102255250  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102245641  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102252210  RPS6KA5; ribosomal protein S6 kinase A5 [KO:K04445] [EC:2.7.11.1]
102246867  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
102241887  ATF2; activating transcription factor 2 [KO:K04450]
102238786  ATF4; activating transcription factor 4 [KO:K04374]
102258024  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
102241829  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
102244833  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
102245296  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
102251355  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
102240701  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
102261840  ATF6B; activating transcription factor 6 beta [KO:K09049]
102252371  CREM; cAMP responsive element modulator [KO:K09052]
102248597  BCL2; BCL2, apoptosis regulator [KO:K02161]
102257237  RAPGEF3; Rap guanine nucleotide exchange factor 3 [KO:K08014]
102262528  RAPGEF4; Rap guanine nucleotide exchange factor 4 [KO:K04351]
102254628  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102248097  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102254920  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
106723559  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102249318  GNAI2; G protein subunit alpha i2 [KO:K04630]
102239557  GNAI3; G protein subunit alpha i3 [KO:K04630]
102256872  GNAI1; G protein subunit alpha i1 [KO:K04630]
102241723  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
102246489  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
102246179  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
102254864  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102254191  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102251050  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
myb04020  Calcium signaling pathway
myb04151  PI3K-Akt signaling pathway
myb04260  Cardiac muscle contraction
KO pathway
ko04261   
LinkDB

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