KEGG   PATHWAY: lcat04261
Entry
lcat04261                   Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Lemur catta (Ring-tailed lemur)
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
lcat04261  Adrenergic signaling in cardiomyocytes
lcat04261

Other DBs
GO: 0001997
Organism
Lemur catta (Ring-tailed lemur) [GN:lcat]
Gene
123650240  ADRB1; beta-1 adrenergic receptor [KO:K04141]
123638093  ADRB2; beta-2 adrenergic receptor [KO:K04142]
123622308  neuroendocrine secretory protein 55-like [KO:K04632]
123622310  guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
123647256  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
123648063  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
123636670  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
123650680  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
123630472  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
123640442  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
123625466  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
123644339  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
123632319  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
123633110  BVES; blood vessel epicardial substance [KO:K21108]
123630510  POPDC2; popeye domain-containing protein 2 isoform X1 [KO:K26206]
123633111  POPDC3; popeye domain-containing protein 3 [KO:K26207]
123627049  KCNK2; potassium channel subfamily K member 2 isoform X1 [KO:K04913]
123637748  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
123635476  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
123624054  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
123635097  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
123635182  sodium/potassium-transporting ATPase subunit alpha-2 isoform X1 [KO:K01539] [EC:7.2.2.13]
123635183  sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
123628796  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
123630115  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
123635337  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
123650896  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
123641530  FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538]
123634341  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
123642922  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
123642801  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
123628453  ATP2B3; LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 3 [KO:K05850] [EC:7.2.2.10]
123638112  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
123639459  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
123627012  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
123636834  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
123623895  SLC8A2; sodium/calcium exchanger 2 isoform X1 [KO:K05849]
123640278  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
123627092  SCN5A; sodium channel protein type 5 subunit alpha [KO:K04838]
123643648  SCN7A; sodium channel protein type 7 subunit alpha [KO:K04839]
123624497  SCN1B; sodium channel subunit beta-1 [KO:K04845]
123641972  SCN4B; sodium channel subunit beta-4 [KO:K04848]
123640189  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
123623167  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
123628833  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
123626819  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
123620820  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
123625737  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
123640441  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
123643468  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
123647164  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858]
123623233  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859]
123623160  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
123640621  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
123650652  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
123640483  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
123632491  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
123620213  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
123650651  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
123624657  CACNG6; voltage-dependent calcium channel gamma-6 subunit isoform X1 [KO:K04871]
123624656  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
123624185  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
123636893  CALM2; calmodulin-2 [KO:K02183]
123645611  CALM1; calmodulin-1 [KO:K02183]
123623035  CALML3; calmodulin-like protein 3 [KO:K02183]
123623036  CALML5; calmodulin-like protein 5 [KO:K02183]
123631755  CALML4; calmodulin-like protein 4 [KO:K02183]
123623919  CALM3; calmodulin-3 [KO:K02183]
123634905  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
123636681  calmodulin-alpha-like [KO:K02183]
123638072  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
123647608  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
123650285  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
123627700  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
123627597  RYR2; ryanodine receptor 2 isoform X1 [KO:K04962]
123637775  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
123633863  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform-like [KO:K04382] [EC:3.1.3.16]
123626658  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
123624632  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
123641707  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
123622192  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
123637931  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
123626639  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
123650004  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
123628382  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
123629279  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
123650175  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
123622540  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
123631894  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
123648241  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
123641399  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
123627069  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
123626056  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
123642855  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
123636756  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
123623191  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
123624691  TNNI3; troponin I, cardiac muscle [KO:K12044]
123626933  TNNT2; troponin T, cardiac muscle isoform X1 [KO:K12045]
123630671  TPM1; tropomyosin alpha-1 chain isoform X1 [KO:K10373]
123646159  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
123634014  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
123637914  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
123621825  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
123620271  myosin-6 [KO:K17751]
123620275  MYH7; myosin-7 [KO:K17751]
123626055  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
123623144  MYL3; myosin light chain 3 [KO:K12749]
123620571  MYL4; myosin light chain 4 isoform X1 [KO:K12750]
123633210  PLN; cardiac phospholamban [KO:K05852]
123632523  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
123626067  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1 [KO:K05853] [EC:7.2.2.10]
123620633  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
123627605  AGT; LOW QUALITY PROTEIN: angiotensinogen [KO:K09821]
123630151  AGTR1; type-1 angiotensin II receptor [KO:K04166]
123628545  AGTR2; type-2 angiotensin II receptor [KO:K04167]
123626643  ADRA1A; alpha-1A adrenergic receptor isoform X1 [KO:K04135]
123638882  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
123622561  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
123646308  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
123622057  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
123622065  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
123624366  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
123641430  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
123621118  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
123639725  PPP1R1A; protein phosphatase 1 regulatory subunit 1A isoform X1 [KO:K08050]
123632778  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
123626228  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123645483  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
123644073  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
123643408  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
123640339  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
123646158  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
123647675  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
123633885  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
123634008  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
123642645  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
123647634  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
123631772  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
123626456  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
123621883  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
123640470  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014]
123644044  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
123632869  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
123632871  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
123640770  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
123640771  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
123623249  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
123647150  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
123635002  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
123647726  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
123650941  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
123650942  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
123624322  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123627566  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123643797  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
lcat04020  Calcium signaling pathway
lcat04151  PI3K-Akt signaling pathway
lcat04260  Cardiac muscle contraction
KO pathway
ko04261   
LinkDB

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