KEGG   PATHWAY: lve04261
Entry
lve04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Lipotes vexillifer (Yangtze River dolphin)
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
lve04261  Adrenergic signaling in cardiomyocytes
lve04261

Other DBs
GO: 0001997
Organism
Lipotes vexillifer (Yangtze River dolphin) [GN:lve]
Gene
103082012  ADRB1; beta-1 adrenergic receptor [KO:K04141]
103071524  ADRB2; beta-2 adrenergic receptor [KO:K04142]
103089051  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
103085385  neuroendocrine secretory protein 55-like [KO:K04632]
103081539  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
103084817  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
103076182  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
103075499  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
103091169  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
103075153  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
103078677  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
103085845  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
103070451  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
103073815  BVES; blood vessel epicardial substance isoform X1 [KO:K21108]
103087332  POPDC2; popeye domain-containing protein 2 isoform X1 [KO:K26206]
103073539  POPDC3; popeye domain-containing protein 3 [KO:K26207]
103089238  KCNK2; potassium channel subfamily K member 2-like isoform X1 [KO:K04913]
103077464  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103074112  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
103085693  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
103074614  ATP1A4; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
103074894  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 isoform X1 [KO:K01539] [EC:7.2.2.13]
103068908  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
103068907  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 isoform X1 [KO:K01540]
103089616  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
103084463  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
103089387  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
103083053  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
103086857  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
103075489  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
103088376  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
103070670  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
103085203  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
103078806  ATP2B1; plasma membrane calcium-transporting ATPase 1 [KO:K05850] [EC:7.2.2.10]
103074445  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
103085990  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
103080144  sodium/calcium exchanger 3-like [KO:K05849]
103071162  SCN5A; sodium channel protein type 5 subunit alpha isoform X1 [KO:K04838]
103085392  SCN7A; LOW QUALITY PROTEIN: sodium channel protein type 7 subunit alpha [KO:K04839]
103088972  SCN1B; sodium channel subunit beta-1 [KO:K04845]
103072034  SCN4B; sodium channel subunit beta-4 [KO:K04848]
103087340  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
103074544  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
103082192  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
103090575  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
103070949  CACNB1; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit beta-1 [KO:K04862]
103079439  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
103075622  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
103089902  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
103082365  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 [KO:K04858]
103076085  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859]
103076318  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
103076342  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
103073774  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
103089907  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
103090977  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
103073501  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
103087746  CACNG6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871]
103086371  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
103088020  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
103091655  CALM3; calmodulin [KO:K02183]
103079915  CALML6; calmodulin-like protein 6 [KO:K02183]
103080762  CALM1; calmodulin isoform X1 [KO:K02183]
103087479  CALM2; calmodulin [KO:K02183]
103072156  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
103074541  LOW QUALITY PROTEIN: calmodulin-like protein 1-like [KO:K02183]
103074817  CALML5; calmodulin-like protein 5 [KO:K02183]
103088458  CAMK2D; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
103075213  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
103072903  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
103081366  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
103085414  RYR2; ryanodine receptor 2-like [KO:K04962]
103086967  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
103074714  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
103082213  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like isoform X1 [KO:K03456]
103068746  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
103075527  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
103090378  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
103070944  PPP2R2C; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform [KO:K04354]
103085298  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
103086552  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
103087752  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
103090518  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
103077162  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
103069560  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
103087914  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
103079037  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
103074623  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
103086084  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit B-like [KO:K06269] [EC:3.1.3.16]
103072994  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
103074387  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
103080471  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
103087809  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
103083728  TNNI3; troponin I, cardiac muscle [KO:K12044]
103068355  TNNT2; troponin T, cardiac muscle [KO:K12045]
103084698  TPM1; tropomyosin alpha-4 chain isoform X1 [KO:K10373]
103084875  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
103082412  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
103089632  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
103074529  ACTC1; actin, alpha cardiac muscle 1 isoform X1 [KO:K12314]
103090453  MYH7; myosin-7 [KO:K17751]
103090716  MYH6; myosin-6 [KO:K17751]
103077775  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
103085123  MYL3; myosin light chain 3 [KO:K12749]
103069828  MYL4; myosin light chain 4 isoform X1 [KO:K12750]
103081226  PLN; cardiac phospholamban [KO:K05852]
103082480  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
103074209  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
103068766  ATP2A2; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
103078157  AGT; angiotensinogen [KO:K09821]
103090648  AGTR1; type-1 angiotensin II receptor [KO:K04166]
103072424  AGTR2; type-2 angiotensin II receptor-like [KO:K04167]
103084741  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
103083430  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
103073579  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
103082420  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
103086280  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
103083884  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
103078639  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
103079287  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
103073028  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
103073079  PPP1R1A; protein phosphatase 1 regulatory subunit 1A [KO:K08050]
103070260  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
103075543  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103080020  RPS6KA5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:2.7.11.1]
103075978  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
103089070  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
103083306  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
103086171  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
103085711  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
103087008  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
103091030  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
103071696  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
103081811  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
103069101  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
103075623  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
103077294  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
103080613  RAPGEF3; rap guanine nucleotide exchange factor 3 [KO:K08014]
103078675  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
103083209  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103077530  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103078049  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103078710  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103080185  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
103077308  GNAI2; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
103081367  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
103069455  PIK3CG; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
103076917  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
103076642  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
103084975  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103076365  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103068921  AKT3; RAC-gamma 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
lve04020  Calcium signaling pathway
lve04151  PI3K-Akt signaling pathway
lve04260  Cardiac muscle contraction
KO pathway
ko04261   
LinkDB

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