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KEGG   PATHWAY: fpg04261
Entry
fpg04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Falco peregrinus (peregrine 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
fpg04261  Adrenergic signaling in cardiomyocytes
fpg04261

Other DBs
GO: 0001997
Organism
Falco peregrinus (peregrine falcon) [GN:fpg]
Gene
101910581  RAPGEF4; Rap guanine nucleotide exchange factor 4 [KO:K04351]
101910692  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
101910831  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
101910912  sarcoplasmic/endoplasmic reticulum calcium ATPase 1-like [KO:K05853] [EC:7.2.2.10]
101910975  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
101911020  MYL3; myosin light chain 3 [KO:K12749]
101911235  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
101911269  potassium voltage-gated channel subfamily KQT member 1-like [KO:K04926]
101911510  PLN; phospholamban [KO:K05852]
101911529  ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853] [EC:7.2.2.10]
101911642  SLC9A1; solute carrier family 9 member A1 [KO:K05742]
101911647  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
101911755  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
101911904  CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867]
101912040  ATF2; activating transcription factor 2 [KO:K04450]
101912097  CALML4; calmodulin like 4 [KO:K02183]
101912140  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101912258  ADRA1D; adrenoceptor alpha 1D [KO:K04137]
101912415  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
101912464  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101912795  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
101913094  ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:7.2.2.10]
101913219  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
101913302  TPM2; tropomyosin 2 (beta) [KO:K10374]
101913442  RYR2; ryanodine receptor 2 [KO:K04962]
101913634  BVES; blood vessel epicardial substance [KO:K21108]
101913700  SLC8A3; solute carrier family 8 member A3 [KO:K05849]
101913968  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
101914389  ATP2B4; ATPase plasma membrane Ca2+ transporting 4 [KO:K05850] [EC:7.2.2.10]
101914397  AGTR1; angiotensin II receptor type 1 [KO:K04166]
101914593  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
101914605  POPDC2; popeye domain containing 2 [KO:K26206]
101914611  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101914615  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
101914699  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
101914764  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
101914769  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
101914787  ATP1A1; ATPase Na+/K+ transporting subunit alpha 1 [KO:K01539] [EC:7.2.2.13]
101914877  CACNG4; calcium voltage-gated channel auxiliary subunit gamma 4 [KO:K04869]
101914921  ACTC1; actin, alpha, cardiac muscle 1 [KO:K12314]
101915017  ATP1A2; ATPase Na+/K+ transporting subunit alpha 2 [KO:K01539] [EC:7.2.2.13]
101915075  ATP2B2; ATPase plasma membrane Ca2+ transporting 2 [KO:K05850] [EC:7.2.2.10]
101915262  CACNB1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04863]
101915367  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
101915392  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
101915802  PPP2R3A; protein phosphatase 2 regulatory subunit B''alpha [KO:K11583]
101915893  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
101915966  actin, alpha skeletal muscle B-like [KO:K12314]
101916036  SCN4B; sodium voltage-gated channel beta subunit 4 [KO:K04848]
101916082  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
101916106  CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864]
101916160  CACNA2D3; calcium voltage-gated channel auxiliary subunit alpha2delta 3 [KO:K04860]
101916251  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
101916278  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
101916384  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
101916431  TNNT2; troponin T2, cardiac type [KO:K12045]
101916533  MYL2; myosin light chain 2 [KO:K10351]
101916622  CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863]
101916649  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
101916694  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
101916711  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
101916818  CALM2; calmodulin 2 [KO:K02183]
101916833  PPP2R3C; protein phosphatase 2 regulatory subunit B''gamma [KO:K11583]
101917007  CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858]
101917014  KCNE1; potassium voltage-gated channel subfamily E regulatory subunit 1 [KO:K04894]
101917348  ADRB1; adrenoceptor beta 1 [KO:K04141]
101917737  uncharacterized LOC101917737 [KO:K01540]
101917880  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101918283  TPM3; tropomyosin 3 [KO:K09290]
101918398  KCNQ1; potassium voltage-gated channel subfamily Q member 1 [KO:K04926]
101918521  GNAI3; G protein subunit alpha i3 [KO:K04630]
101918751  SCN5A; sodium voltage-gated channel alpha subunit 5 [KO:K04838]
101918822  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
101918846  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
101918868  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
101918928  CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865]
101918953  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
101919099  CALM1; calmodulin 1 [KO:K02183]
101919126  AGTR2; angiotensin II receptor type 2 [KO:K04167]
101919188  TNNC1; troponin C1, slow skeletal and cardiac type [KO:K05865]
101919264  RPS6KA5; ribosomal protein S6 kinase A5 [KO:K04445] [EC:2.7.11.1]
101919502  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
101919673  CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861]
101919681  POPDC3; popeye domain containing 3 [KO:K26207]
101919694  SLC8A2; solute carrier family 8 member A2 [KO:K05849]
101919808  MYH6; myosin-6 [KO:K17751]
101919810  ADRB2; adrenoceptor beta 2 [KO:K04142]
101920124  AGT; angiotensinogen [KO:K09821]
101920170  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
101920293  CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859]
101920353  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101920362  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
101920743  CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868]
101920842  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
101920857  ADRA1B; adrenoceptor alpha 1B [KO:K04136]
101921274  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
101921428  PPP2R3B; protein phosphatase 2 regulatory subunit B''beta [KO:K11583]
101921528  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
101921567  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
101921635  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
101921697  TPM4; tropomyosin alpha-4 chain [KO:K10375]
101921728  BCL2; BCL2, apoptosis regulator [KO:K02161]
101921738  PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
101921768  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
101921803  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
101921834  ATF4; activating transcription factor 4 [KO:K04374]
101921932  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
101922071  voltage-dependent L-type calcium channel subunit alpha-1F-like [KO:K04853]
101922194  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
101922203  sodium channel protein type 5 subunit alpha-like [KO:K04838]
101922321  GNAS; GNAS complex locus [KO:K04632]
101922323  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
101922366  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
101922433  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101922583  SLC8A1; solute carrier family 8 member A1 [KO:K05849]
101922617  TPM1; tropomyosin 1 (alpha) [KO:K10373]
101922621  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
101922673  ATP2B1; ATPase plasma membrane Ca2+ transporting 1 [KO:K05850] [EC:7.2.2.10]
101923358  CACNG5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870]
101923465  myosin light chain, embryonic [KO:K12750]
101923535  CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866]
101923570  ADRA1A; adrenoceptor alpha 1A [KO:K04135]
101923695  CREM; cAMP responsive element modulator [KO:K09052]
101923747  calmodulin, striated muscle [KO:K02183]
101923748  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
101923937  KCNK2; potassium two pore domain channel subfamily K member 2 [KO:K04913]
101924330  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
101924346  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
101924432  PPP1R1A; protein phosphatase 1 regulatory inhibitor subunit 1A [KO:K08050]
101924469  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
101924636  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
101924787  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
101924920  GNAI2; G protein subunit alpha i2 [KO:K04630]
101924930  RAPGEF3; Rap guanine nucleotide exchange factor 3 [KO:K08014]
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
fpg04020  Calcium signaling pathway
fpg04260  Cardiac muscle contraction
KO pathway
ko04261   

  All links  
Genome (1)   
   KEGG GENOME (1)   
Gene (134)   
   KEGG GENES (134)   
All databases (135)   

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