KEGG   PATHWAY: fch04261
Entry
fch04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Falco cherrug (Saker falcon)
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
fch04261  Adrenergic signaling in cardiomyocytes
fch04261

Other DBs
GO: 0001997
Organism
Falco cherrug (Saker falcon) [GN:fch]
Gene
102052904  ADRB1; LOW QUALITY PROTEIN: beta-1 adrenergic receptor [KO:K04141]
102054857  ADRB2; beta-2 adrenergic receptor [KO:K04142]
102059934  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
102056699  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
102049688  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
102047195  ADCY3; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
102049855  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
102050328  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
102052224  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
102056487  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
102047847  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
102046855  BVES; LOW QUALITY PROTEIN: blood vessel epicardial substance [KO:K21108]
102050083  POPDC2; popeye domain-containing protein 2 isoform X2 [KO:K26206]
102055556  KCNK2; potassium channel subfamily K member 2 isoform X1 [KO:K04913]
102052736  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102050259  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
102059303  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
102053971  ATP1B4; protein ATP1B4 [KO:K01540]
102048230  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
102050299  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X2 [KO:K01540]
114015464  FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538]
102059778  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
102057915  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
102058980  potassium voltage-gated channel subfamily KQT member 1-like [KO:K04926]
102057571  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
102053029  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X5 [KO:K05850] [EC:7.2.2.10]
102057091  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
102046062  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
102050111  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
102051074  SLC8A1; sodium/calcium exchanger 1 [KO:K05849]
102049307  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
102048607  sodium channel protein type 5 subunit alpha isoform X1 [KO:K04838]
102049132  sodium channel protein type 5 subunit alpha-like [KO:K04838]
114015471  SCN4B; sodium channel subunit beta-4 [KO:K04848]
102048150  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
102054190  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
102046341  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F-like [KO:K04853]
102058184  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X11 [KO:K04857]
102052181  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X7 [KO:K04863]
102054191  CACNB4; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit beta-4 [KO:K04865]
102059307  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X9 [KO:K04858]
102049917  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859]
102054020  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860]
102054748  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X1 [KO:K04861]
102050112  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
102057094  CACNG2; voltage-dependent calcium channel gamma-2 subunit isoform X1 [KO:K04867]
102047196  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
102049937  voltage-dependent calcium channel gamma-5 subunit isoform X2 [KO:K04870]
102049336  uncharacterized protein LOC102049336 [KO:K04873]
102049588  CALM1; calmodulin-1 [KO:K02183]
102058651  CALM2; calmodulin-2 [KO:K02183]
102058709  calmodulin, striated muscle [KO:K02183]
102055619  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
102052104  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
102057655  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
102051471  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
102053979  RYR2; ryanodine receptor 2 [KO:K04962]
102052989  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102058381  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102056197  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
102047212  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X2 [KO:K04354]
102053115  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
102050344  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
102050692  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
102045690  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
102049772  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
102051836  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
102057631  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X3 [KO:K11584]
102055426  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
102053998  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
102059701  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
102058478  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
102054093  serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
102053170  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
102051061  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
102060000  TNNT2; troponin T, cardiac muscle [KO:K12045]
102055413  TPM1; tropomyosin alpha-1 chain isoform X10 [KO:K10373]
102059681  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
102057451  TPM3; tropomyosin alpha-3 chain isoform X6 [KO:K09290]
102055978  TPM4; tropomyosin alpha-4 chain [KO:K10375]
102050360  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
102051901  actin, alpha skeletal muscle B-like [KO:K12314]
102046529  MYL2; LOW QUALITY PROTEIN: myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
102053884  MYL3; myosin light chain 3 [KO:K12749]
102047288  MYL4; myosin light chain 4 [KO:K12750]
102055282  PLN; cardiac phospholamban [KO:K05852]
102054337  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
102050086  ATP2A2; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
102055915  sarcoplasmic/endoplasmic reticulum calcium ATPase 1-like [KO:K05853] [EC:7.2.2.10]
102048720  AGT; angiotensinogen [KO:K09821]
102052791  AGTR1; type-1 angiotensin II receptor [KO:K04166]
102051411  AGTR2; type-2 angiotensin II receptor [KO:K04167]
102049705  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
102047141  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
102051126  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
102046812  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102048018  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
102054421  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
102048448  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
102053069  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
102048357  PPP1R1A; LOW QUALITY PROTEIN: protein phosphatase 1 regulatory subunit 1A [KO:K08050]
102048221  MAPK1; LOW QUALITY PROTEIN: mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102049415  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
102050642  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
102052727  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
102049324  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102055433  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
102060195  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
102049519  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
102052762  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
102055392  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
102057248  CREM; cAMP-responsive element modulator isoform X5 [KO:K09052]
102056589  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
102048878  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014]
102051155  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
102059377  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102054359  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
102051874  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
102052038  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102051232  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
102059982  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
102056299  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
102051392  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X2 [KO:K21289] [EC:2.7.1.153]
102058745  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
102058572  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X2 [KO:K21290]
102060018  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102055811  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102050094  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
fch04020  Calcium signaling pathway
fch04260  Cardiac muscle contraction
KO pathway
ko04261   
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