KEGG   PATHWAY: ctig04261
Entry
ctig04261                   Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Crotalus tigris (Tiger rattlesnake)
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
ctig04261  Adrenergic signaling in cardiomyocytes
ctig04261

Other DBs
GO: 0001997
Organism
Crotalus tigris (Tiger rattlesnake) [GN:ctig]
Gene
120312256  ADRB1; beta-1 adrenergic receptor isoform X1 [KO:K04141]
120312076  ADRB2; beta-2 adrenergic receptor [KO:K04142]
120317707  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
120312767  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
120301698  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
120309099  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
120314849  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
120311904  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
120302331  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
120312119  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
120304822  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
120315776  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
120311512  BVES; blood vessel epicardial substance isoform X1 [KO:K21108]
120318675  POPDC2; popeye domain-containing protein 2 isoform X1 [KO:K26206]
120311513  POPDC3; popeye domain-containing protein 3 [KO:K26207]
120304963  KCNK2; potassium channel subfamily K member 2 isoform X1 [KO:K04913]
120309375  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
120297855  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
120311998  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
120296669  sodium/potassium-transporting ATPase subunit alpha-2 isoform X1 [KO:K01539] [EC:7.2.2.13]
120316535  sodium/potassium-transporting ATPase subunit alpha-2-like [KO:K01539] [EC:7.2.2.13]
120318645  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
120298584  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
120305712  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 isoform X1 [KO:K01540]
120314390  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
120316609  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
120304097  SLC9A1; sodium/hydrogen exchanger 1 isoform X1 [KO:K05742]
120311356  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 isoform X1 [KO:K04926]
120313054  potassium voltage-gated channel subfamily KQT member 1-like [KO:K04926]
120296702  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
120299657  plasma membrane calcium-transporting ATPase 1-like [KO:K05850] [EC:7.2.2.10]
120306714  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
120307474  ATP2B1; LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 1 [KO:K05850] [EC:7.2.2.10]
120316118  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
120310147  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
120317178  sodium/calcium exchanger 1-like [KO:K05849]
120297837  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
120304181  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
120319861  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
120299446  sodium channel protein type 5 subunit alpha-like isoform X1 [KO:K04838]
120300057  SCN1B; sodium channel subunit beta-1 [KO:K04845]
120307256  SCN4B; sodium channel subunit beta-4 isoform X1 [KO:K04848]
120315478  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
120315892  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
120311308  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
120298959  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
120315147  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
120302761  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
120302349  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 [KO:K04864]
120304625  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
120312564  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858]
120315014  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
120301001  voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
120314872  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X1 [KO:K04861]
120300590  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
120312408  CACNG2; voltage-dependent calcium channel gamma-2 subunit isoform X1 [KO:K04867]
120310839  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
120300558  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
120299993  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
120304482  CACNG6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871]
120304484  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
120304483  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
120317093  calmodulin-1-like [KO:K02183]
120299563  CALM2; calmodulin-2 [KO:K02183]
120299854  CALM3; calmodulin-3 [KO:K02183]
120309567  CALM1; calmodulin-1 [KO:K02183]
120319244  CALML6; calmodulin-like protein 6 [KO:K02183]
120320134  CALML4; calmodulin-like protein 4 [KO:K02183]
120306873  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
120313925  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
120315521  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
120316087  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
120318826  RYR2; ryanodine receptor 2 isoform X1 [KO:K04962]
120305511  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
120303758  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
120298685  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
120305493  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
120311782  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
120312883  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
120316221  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
120311823  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
120313921  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
120297227  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
120299569  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
120317864  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
120314903  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
120315374  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
120297154  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
120305346  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
120306948  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
120316695  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
120312765  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
120304515  TNNI3; troponin I, cardiac muscle [KO:K12044]
120301775  TNNT2; troponin T, cardiac muscle isoform X1 [KO:K12045]
120306573  TPM1; tropomyosin alpha-1 chain isoform X1 [KO:K10373]
120317190  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
120319775  TPM2; tropomyosin beta chain isoform X1 [KO:K09290]
120305959  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
120304881  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
120314109  actin, alpha skeletal muscle B-like isoform X1 [KO:K12314]
120305795  MYH7; myosin-7 [KO:K17751]
120308897  myosin-6-like [KO:K17751]
120316716  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
120318044  MYL3; myosin light chain 3 [KO:K12749]
120315199  MYL4; myosin light chain 4 [KO:K12750]
120313504  PLN; cardiac phospholamban [KO:K05852]
120304560  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
120304272  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
120316704  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1 [KO:K05853] [EC:7.2.2.10]
120317656  AGT; angiotensinogen [KO:K09821]
120313107  AGTR1; type-1 angiotensin II receptor [KO:K04166]
120313118  AGTR2; type-2 angiotensin II receptor [KO:K04167]
120312875  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
120310212  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
120316041  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
120317177  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
120307675  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
120315294  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
120315307  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
120300008  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
120308540  PPP1R1A; protein phosphatase 1 regulatory subunit 1A isoform X1 [KO:K08050]
120303124  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
120304407  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
120309570  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
120312318  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
120306308  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
120304664  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
120317070  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
120305411  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
120308558  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
120314937  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
120319804  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
120307325  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
120305189  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
120306024  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
120297252  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
120312211  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014]
120316341  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
120298965  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
120298976  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
120306032  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
120306038  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
120298914  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
120299803  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
120303834  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
120313008  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
120313314  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
120313315  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
120312169  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120316371  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120318620  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
ctig04020  Calcium signaling pathway
ctig04260  Cardiac muscle contraction
KO pathway
ko04261   
LinkDB

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