KEGG   PATHWAY: gja04261
Entry
gja04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Gekko japonicus (Schlegel's Japanese gecko)
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
gja04261  Adrenergic signaling in cardiomyocytes
gja04261

Other DBs
GO: 0001997
Organism
Gekko japonicus (Schlegel's Japanese gecko) [GN:gja]
Gene
107122433  ADRB1; adrenoceptor beta 1 [KO:K04141]
107106463  ADRB2; adrenoceptor beta 2 [KO:K04142]
107119835  GNAS; GNAS complex locus [KO:K04632]
107119176  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
107108835  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
107124706  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
107111738  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
107113906  adenylate cyclase type 5-like [KO:K08045] [EC:4.6.1.1]
107120916  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
107117185  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
107119214  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
107109291  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
107124358  popeye domain-containing protein 3 [KO:K21108]
107109353  POPDC2; popeye domain containing 2 [KO:K26206]
107125653  KCNK2; potassium two pore domain channel subfamily K member 2 [KO:K04913]
107117304  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
107117579  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
107122231  sodium/potassium-transporting ATPase subunit alpha-3-like [KO:K01539] [EC:7.2.2.13]
107126069  sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
107109259  ATP1A1; ATPase Na+/K+ transporting subunit alpha 1 [KO:K01539] [EC:7.2.2.13]
107121089  ATP1B2; ATPase Na+/K+ transporting subunit beta 2 [KO:K01540]
107110300  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
107123739  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
107112362  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
107110810  SLC9A1; solute carrier family 9 member A1 [KO:K05742]
107118587  KCNQ1; potassium voltage-gated channel subfamily Q member 1 [KO:K04926]
107120674  KCNE1; potassium voltage-gated channel subfamily E regulatory subunit 1 [KO:K04894]
107120494  plasma membrane calcium-transporting ATPase 1-like [KO:K05850] [EC:7.2.2.10]
107107093  ATP2B4; ATPase plasma membrane Ca2+ transporting 4 [KO:K05850] [EC:7.2.2.10]
107106293  plasma membrane calcium-transporting ATPase 3-like [KO:K05850] [EC:7.2.2.10]
107124162  plasma membrane calcium-transporting ATPase 2-like [KO:K05850] [EC:7.2.2.10]
107113942  ATP2B1; ATPase plasma membrane Ca2+ transporting 1 [KO:K05850] [EC:7.2.2.10]
107107692  SLC8A3; solute carrier family 8 member A3 [KO:K05849]
107115194  sodium/calcium exchanger 1-like [KO:K05849]
107119826  SLC8A1; solute carrier family 8 member A1 [KO:K05849]
107111187  sodium channel protein type 5 subunit alpha-like [KO:K04838]
107119869  SCN1B; sodium voltage-gated channel beta subunit 1 [KO:K04845]
107116779  SCN4B; sodium voltage-gated channel beta subunit 4 [KO:K04848]
107120231  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
107116832  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
107117359  voltage-dependent L-type calcium channel subunit alpha-1F-like [KO:K04853]
107110972  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
107118450  CACNB1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04862]
107113294  CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863]
107120883  CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864]
107125599  CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865]
107124567  CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858]
107116010  CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859]
107109400  CACNA2D3; calcium voltage-gated channel auxiliary subunit alpha2delta 3 [KO:K04860]
107120232  CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861]
107107951  CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866]
107123263  CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867]
107106275  CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868]
107107946  CACNG4; calcium voltage-gated channel auxiliary subunit gamma 4 [KO:K04869]
107107943  CACNG5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870]
107113141  CACNG6; calcium voltage-gated channel auxiliary subunit gamma 6 [KO:K04871]
107113155  CACNG7; calcium voltage-gated channel auxiliary subunit gamma 7 [KO:K04872]
107113126  CACNG8; calcium voltage-gated channel auxiliary subunit gamma 8 [KO:K04873]
107117539  CALM3; calmodulin 3 [KO:K02183]
107113282  CALML4; calmodulin like 4 [KO:K02183]
107116092  CALML6; calmodulin like 6 [KO:K02183]
107115205  calmodulin [KO:K02183]
107120542  CALM1; calmodulin 1 [KO:K02183]
107110993  CALM2; calmodulin 2 [KO:K02183]
107110299  calcium/calmodulin-dependent protein kinase type II delta chain [KO:K04515] [EC:2.7.11.17]
107117391  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
107122036  calcium/calmodulin-dependent protein kinase type II subunit gamma-like [KO:K04515] [EC:2.7.11.17]
107123332  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
107120023  ryanodine receptor 2-like [KO:K04962]
107125982  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
107110575  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
107124393  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
107126265  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
107108836  PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
107112470  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
107121378  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
107114806  PPP2R3C; protein phosphatase 2 regulatory subunit B''gamma [KO:K11583]
107110228  PPP2R3B; protein phosphatase 2 regulatory subunit B''beta [KO:K11583]
107123594  PPP2R3A; protein phosphatase 2 regulatory subunit B''alpha [KO:K11583]
107116652  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
107123087  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
107124204  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
107110121  PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
107124785  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
107124492  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
107112146  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
107118515  TNNC1; troponin C1, slow skeletal and cardiac type [KO:K05865]
107118434  TNNI3; troponin I3, cardiac type [KO:K12044]
107114778  TNNT2; troponin T2, cardiac type [KO:K12045]
107117899  TPM1; tropomyosin 1 (alpha) [KO:K10373]
107117103  tropomyosin alpha-3 chain [KO:K09290]
107117066  tropomyosin alpha-3 chain-like [KO:K09290]
107121701  TPM4; tropomyosin 4 [KO:K10375]
107118263  actin, alpha cardiac muscle 1-like [KO:K12314]
107121602  actin, alpha cardiac muscle 1 [KO:K12314]
107107576  myosin-7-like [KO:K17751]
107105618  myosin-6 [KO:K17751]
107112184  MYL2; myosin light chain 2 [KO:K10351]
107123952  myosin light chain 1, cardiac muscle [KO:K12749]
107118448  MYL4; myosin light chain 4 [KO:K12750]
107108622  PLN; phospholamban [KO:K05852]
107107698  sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
107122681  ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:7.2.2.10]
107115908  ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:7.2.2.10]
107119021  AGT; angiotensinogen [KO:K09821]
107124666  AGTR1; angiotensin II receptor type 1 [KO:K04166]
107114688  AGTR2; angiotensin II receptor type 2 [KO:K04167]
107111679  alpha-1A adrenergic receptor-like [KO:K04135]
107110395  ADRA1D; adrenoceptor alpha 1D [KO:K04137]
107116527  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107106753  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
107115177  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
107123894  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
107119642  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
107122708  protein phosphatase 1 regulatory subunit 1A-like [KO:K08050]
107117455  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
107115252  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107113343  RPS6KA5; ribosomal protein S6 kinase A5 [KO:K04445] [EC:2.7.11.1]
107105893  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
107123397  ATF2; activating transcription factor 2 [KO:K04450]
107117129  ATF4; activating transcription factor 4 [KO:K04374]
107107817  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
107110879  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
107121734  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
107118239  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
107120250  cyclic AMP-responsive element-binding protein 3-like [KO:K09048]
107105766  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
107118458  ATF6B; activating transcription factor 6 beta [KO:K09049]
107105524  CREM; cAMP responsive element modulator [KO:K09052]
107108130  apoptosis regulator Bcl-2-like [KO:K02161]
107109551  RAPGEF3; Rap guanine nucleotide exchange factor 3 [KO:K08014]
107107055  RAPGEF4; Rap guanine nucleotide exchange factor 4 [KO:K04351]
107110949  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
107110955  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
107110975  mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
107119112  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
107118867  GNAI2; G protein subunit alpha i2 [KO:K04630]
107120788  GNAI3; G protein subunit alpha i3 [KO:K04630]
107121247  GNAI1; G protein subunit alpha i1 [KO:K04630]
107108982  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
107123852  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
107123847  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
107108180  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
107107366  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
107121519  RAC-gamma 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
gja04020  Calcium signaling pathway
gja04260  Cardiac muscle contraction
KO pathway
ko04261   
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