KEGG   PATHWAY: lmut04261
Entry
lmut04261                   Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Lagopus muta (rock ptarmigan)
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
lmut04261  Adrenergic signaling in cardiomyocytes
lmut04261

Other DBs
GO: 0001997
Organism
Lagopus muta (rock ptarmigan) [GN:lmut]
Gene
125693191  ADRB1; beta-1 adrenergic receptor [KO:K04141]
125700281  ADRB2; beta-2 adrenergic receptor [KO:K04142]
125701503  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
125690968  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
125690720  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
125689755  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
125697126  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
125699136  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
125690991  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
125700673  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
125689094  LOW QUALITY PROTEIN: uncharacterized protein LOC125689094 [KO:K21108]
125687988  POPDC2; popeye domain-containing protein 2 isoform X1 [KO:K26206]
125689551  KCNK2; potassium channel subfamily K member 2 isoform X1 [KO:K04913]
125694172  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
125685661  LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-2-like [KO:K01539] [EC:7.2.2.13]
125687968  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
125684636  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
125697594  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
125699679  ATP1B4; protein ATP1B4 [KO:K01540]
125703891  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
125694858  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
125699882  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
125684077  plasma membrane calcium-transporting ATPase 4-like isoform X1 [KO:K05850] [EC:7.2.2.10]
125698904  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
125688452  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
125689936  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
125695407  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
125695836  sodium channel protein type 5 subunit alpha-like isoform X1 [KO:K04838]
125703724  SCN4B; sodium channel subunit beta-4 isoform X1 [KO:K04848]
125693421  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
125698969  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
125687783  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F-like [KO:K04853]
125683997  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
125684739  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
125695684  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
125696956  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
125687995  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858]
125698548  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859]
125698970  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860]
125694751  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
125702319  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
125693312  CACNG2; voltage-dependent calcium channel gamma-2 subunit isoform X1 [KO:K04867]
125700897  CACNG3; LOW QUALITY PROTEIN: voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
125702318  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
125702300  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
125689139  CALM2; calmodulin-2 [KO:K02183]
125698103  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
125688231  calmodulin, striated muscle [KO:K02183]
125694720  CALM1; calmodulin-1 [KO:K02183]
125685190  CAMK2B; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
125692621  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
125693507  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
125700173  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
125689502  RYR2; ryanodine receptor 2 isoform X1 [KO:K04962]
125692383  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
125700063  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
125687644  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like [KO:K03456]
125691754  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
125685166  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
125692875  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
125699996  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
125697326  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
125694337  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
125688403  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
125694419  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
125694478  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
125688677  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
125688892  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
125701722  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
125695050  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
125688760  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
125698714  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
125684283  TNNT2; troponin T, cardiac muscle [KO:K12045]
125698035  TPM1; tropomyosin alpha-1 chain isoform X1 [KO:K10373]
125686916  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
125685926  tropomyosin alpha-3 chain isoform X1 [KO:K09290]
125685927  tropomyosin-like [KO:K09290]
125684878  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
125695033  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
125695439  actin, alpha skeletal muscle B isoform X1 [KO:K12314]
125702806  myosin-7-like isoform X1 [KO:K17751]
125687625  myosin-7 [KO:K17751]
125701687  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
125696329  MYL3; myosin light chain 3 [KO:K12749]
125684661  MYL4; myosin light chain 4 [KO:K12750]
125688591  PLN; cardiac phospholamban [KO:K05852]
125701873  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
125702910  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
125689151  AGT; angiotensinogen [KO:K09821]
125697883  AGTR1; type-1 angiotensin II receptor [KO:K04166]
125699881  AGTR2; type-2 angiotensin II receptor [KO:K04167]
125685329  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
125700443  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
125692733  ADRA1D; alpha-1D adrenergic receptor isoform X1 [KO:K04137]
125686805  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
125690171  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
125690172  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
125694452  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
125702349  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
125685382  PPP1R1A; LOW QUALITY PROTEIN: protein phosphatase 1 regulatory subunit 1A [KO:K08050]
125701926  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
125695521  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
125696660  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
125686631  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
125684994  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
125686689  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
125687103  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
125695054  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
125696233  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
125696462  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
125690650  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
125685547  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014]
125696707  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
125684015  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
125684016  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
125691861  mitogen-activated protein kinase 11-like isoform X1 [KO:K04441] [EC:2.7.11.24]
125691943  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
125697026  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
125684109  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
125698797  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
125696977  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
125702226  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
125702294  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
125689872  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125694568  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
lmut04020  Calcium signaling pathway
lmut04260  Cardiac muscle contraction
KO pathway
ko04261   
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