KEGG   PATHWAY: cdk04261
Entry
cdk04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Camelus dromedarius (Arabian camel)
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
cdk04261  Adrenergic signaling in cardiomyocytes
cdk04261

Other DBs
GO: 0001997
Organism
Camelus dromedarius (Arabian camel) [GN:cdk]
Gene
105104750  ADRB1; LOW QUALITY PROTEIN: beta-1 adrenergic receptor [KO:K04141]
105097013  ADRB2; beta-2 adrenergic receptor [KO:K04142]
105095656  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
105095655  neuroendocrine secretory protein 55 [KO:K04632]
105095715  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
105094039  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105100030  ADCY3; adenylate cyclase type 3 isoform X5 [KO:K08043] [EC:4.6.1.1]
105102432  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
105090284  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105103816  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
105097528  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105096450  ADCY8; adenylate cyclase type 8 isoform X2 [KO:K08048] [EC:4.6.1.1]
105099828  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105097141  BVES; blood vessel epicardial substance isoform X1 [KO:K21108]
105090324  POPDC2; popeye domain-containing protein 2 isoform X1 [KO:K26206]
105097140  POPDC3; popeye domain-containing protein 3 [KO:K26207]
105099341  KCNK2; potassium channel subfamily K member 2 isoform X1 [KO:K04913]
105095035  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105100776  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
116147050  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
105100141  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 isoform X1 [KO:K01539] [EC:7.2.2.13]
105089616  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
105090227  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
105086324  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
105092738  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
105098894  ATP1B4; protein ATP1B4 isoform X2 [KO:K01540]
105103012  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
105090183  FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538]
105100703  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
105106340  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 isoform X1 [KO:K04926]
105089849  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
105103904  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
105104496  ATP2B4; LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 4 [KO:K05850] [EC:7.2.2.10]
105093111  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
105094859  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
105098943  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
105103660  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
105084646  SCN5A; sodium channel protein type 5 subunit alpha [KO:K04838]
105091053  SCN7A; sodium channel protein type 7 subunit alpha isoform X1 [KO:K04839]
105088091  SCN1B; sodium channel subunit beta-1 [KO:K04845]
105090178  SCN4B; sodium channel subunit beta-4 [KO:K04848]
105100748  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
105093176  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
105103284  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
105090835  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
105099052  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
105105423  voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
105103791  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
105093727  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X2 [KO:K04865]
105087345  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X4 [KO:K04858]
105087368  CACNA2D2; LOW QUALITY PROTEIN: voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
105089780  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
105102927  CACNA2D4; LOW QUALITY PROTEIN: voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
105092301  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
105105208  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
105094834  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
105092314  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
105092300  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
105103262  CACNG6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871]
105103264  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
105103263  LOW QUALITY PROTEIN: voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
105096001  CALM1; calmodulin-1 [KO:K02183]
105093281  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
105104026  CALM3; calmodulin-3 [KO:K02183]
105105602  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
105092364  CALM2; calmodulin-2 [KO:K02183]
116147086  calmodulin-like [KO:K02183]
105089916  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X8 [KO:K04515] [EC:2.7.11.17]
105098484  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
105092453  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
105092345  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
105088820  ryanodine receptor 2 isoform X1 [KO:K04962]
105090279  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
105095814  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
105094015  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
105092005  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
105085129  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
105102343  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X2 [KO:K04354]
105097761  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X2 [KO:K04354]
105085282  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X3 [KO:K11583]
105103741  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
105094168  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
105088611  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
105086205  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
105102628  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
105105619  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
105099311  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
105098564  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
105104430  PPP1CA; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
105102484  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
105093410  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
105098776  TNNI3; troponin I, cardiac muscle isoform X1 [KO:K12044]
105095823  TPM1; tropomyosin alpha-1 chain isoform X4 [KO:K10373]
105102294  TPM2; tropomyosin beta chain isoform X2 [KO:K10374]
105089246  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
105101819  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
105089985  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
105106562  LOW QUALITY PROTEIN: myosin-6-like [KO:K17751]
105098287  LOW QUALITY PROTEIN: myosin-7 [KO:K17751]
105102482  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
105103584  MYL3; myosin light chain 3 [KO:K12749]
105090430  MYL4; myosin light chain 4 isoform X2 [KO:K12750]
105088346  PLN; cardiac phospholamban [KO:K05852]
105102781  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
105095745  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
105102497  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
105104282  AGT; angiotensinogen [KO:K09821]
105089509  AGTR1; type-1 angiotensin II receptor [KO:K04166]
105093917  AGTR2; type-2 angiotensin II receptor [KO:K04167]
105102306  ADRA1A; alpha-1A adrenergic receptor isoform X2 [KO:K04135]
105099901  ADRA1B; LOW QUALITY PROTEIN: alpha-1B adrenergic receptor [KO:K04136]
105096051  ADRA1D; LOW QUALITY PROTEIN: alpha-1D adrenergic receptor [KO:K04137]
105087414  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
105101292  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
105101500  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105101545  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X4 [KO:K05858] [EC:3.1.4.11]
105096910  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105092299  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
105100998  PPP1R1A; protein phosphatase 1 regulatory subunit 1A [KO:K08050]
105095214  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105102769  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105095956  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
105093562  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870]
105097571  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
105091928  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105089327  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
105106926  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
105105303  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
105091622  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105102288  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105095833  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
105090854  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
105085973  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
105088999  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
105103807  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014]
105091096  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X5 [KO:K04351]
105101337  MAPK13; mitogen-activated protein kinase 13 isoform X2 [KO:K04441] [EC:2.7.11.24]
105101338  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105090355  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
105090356  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
105087520  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
105085647  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
105100375  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
105093031  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
105098995  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
105098997  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
105099264  AKT3; RAC-gamma serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
105104845  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105093393  AKT2; RAC-beta 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
cdk04020  Calcium signaling pathway
cdk04151  PI3K-Akt signaling pathway
cdk04260  Cardiac muscle contraction
KO pathway
ko04261   
LinkDB

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