KEGG   PATHWAY: cbai04261
Entry
cbai04261                   Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Camelus bactrianus (Bactrian 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
cbai04261  Adrenergic signaling in cardiomyocytes
cbai04261

Other DBs
GO: 0001997
Organism
Camelus bactrianus (Bactrian camel) [GN:cbai]
Gene
105080806  ADRB1; beta-1 adrenergic receptor [KO:K04141]
105069859  ADRB2; beta-2 adrenergic receptor [KO:K04142]
105071802  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
105071803  neuroendocrine secretory protein 55 [KO:K04632]
105080525  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
105081234  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105063873  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
105068818  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
105081635  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105076187  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
105074271  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105082946  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
105064797  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105077085  BVES; blood vessel epicardial substance [KO:K21108]
105081595  POPDC2; popeye domain-containing protein 2 isoform X1 [KO:K26206]
105077086  POPDC3; popeye domain-containing protein 3 [KO:K26207]
105064553  KCNK2; potassium channel subfamily K member 2 [KO:K04913]
105075498  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105068302  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
105079466  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
105062463  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
105069515  sodium/potassium-transporting ATPase subunit alpha-2 isoform X1 [KO:K01539] [EC:7.2.2.13]
105069516  sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
105075952  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
105077514  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
105068071  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
105066824  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
105063448  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
105070382  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
105070215  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
105076090  ATP2B3; LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 3 [KO:K05850] [EC:7.2.2.10]
105074573  ATP2B4; plasma membrane calcium-transporting ATPase 4 [KO:K05850] [EC:7.2.2.10]
105067005  ATP2B1; plasma membrane calcium-transporting ATPase 1 [KO:K05850] [EC:7.2.2.10]
105067459  ATP2B2; plasma membrane calcium-transporting ATPase 2 [KO:K05850] [EC:7.2.2.10]
105074715  SLC8A3; sodium/calcium exchanger 3 [KO:K05849]
105078993  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
105062734  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
105061825  SCN5A; sodium channel protein type 5 subunit alpha [KO:K04838]
105081968  SCN7A; sodium channel protein type 7 subunit alpha [KO:K04839]
105065021  SCN1B; sodium channel subunit beta-1 [KO:K04845]
105067825  SCN4B; sodium channel subunit beta-4 isoform X1 [KO:K04848]
105076642  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
105079596  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
105079415  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
105070011  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
105073272  CACNB1; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit beta-1 [KO:K04862]
105079228  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
105076188  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
105079160  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 [KO:K04865]
105062378  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 [KO:K04858]
105080307  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
105079582  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
105076657  CACNA2D4; LOW QUALITY PROTEIN: voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
105063943  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
105073209  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
105073668  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
105063964  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
105063942  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
105074480  CACNG6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871]
105074323  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
105074324  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
105074723  calmodulin-like [KO:K02183]
105079857  CALM1; calmodulin [KO:K02183]
105079032  CALM2; calmodulin [KO:K02183]
105062547  CALM3; calmodulin [KO:K02183]
105069522  CALML4; calmodulin-like protein 4 [KO:K02183]
105071194  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
105080692  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
105075360  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
105074295  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
105067142  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
105075121  RYR2; ryanodine receptor 2 [KO:K04962]
105082124  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
105067621  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
105080043  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
105067189  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
105083253  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
105063763  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
105072609  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
105079146  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
105063244  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
105071682  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
105079939  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
105083790  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
105074656  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
105064526  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
105070655  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
105080605  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
105063807  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
105070330  PPP1CA; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
105080178  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
105074354  TNNI3; troponin I, cardiac muscle [KO:K12044]
105070008  TNNT2; troponin T, cardiac muscle [KO:K12045]
105080445  TPM1; tropomyosin alpha-1 chain [KO:K10373]
105067328  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
105068190  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
105082520  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
105076871  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
105068782  myosin-7 isoform X1 [KO:K17751]
105068784  MYH6; myosin-6 [KO:K17751]
105080603  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
105072924  MYL3; myosin light chain 3 [KO:K12749]
105069805  MYL4; myosin light chain 4 [KO:K12750]
105077171  PLN; cardiac phospholamban [KO:K05852]
105080703  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
105080845  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
105082851  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
105075087  AGT; angiotensinogen [KO:K09821]
105081270  AGTR1; type-1 angiotensin II receptor [KO:K04166]
105062985  AGTR2; type-2 angiotensin II receptor [KO:K04167]
105063808  ADRA1A; alpha-1A adrenergic receptor isoform X1 [KO:K04135]
105065254  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
105083064  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
105067298  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
105077045  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105082996  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
105082997  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
105070632  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
105063941  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
105076319  PPP1R1A; protein phosphatase 1 regulatory subunit 1A [KO:K08050]
105082839  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105069349  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105079861  RPS6KA5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:2.7.11.1]
105072963  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105073454  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
105073101  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105076770  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
105078379  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
105068196  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
105063046  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105067333  CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105082021  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
105074031  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
105078511  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
105073903  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
105076166  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014]
105073438  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
105064175  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
105064176  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105070806  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
105070807  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
105080234  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
105062385  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
105063651  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
105062421  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
105077550  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
105077591  PIK3R5; LOW QUALITY PROTEIN: phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
105079975  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105083596  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105062855  AKT2; RAC-beta 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
cbai04020  Calcium signaling pathway
cbai04151  PI3K-Akt signaling pathway
cbai04260  Cardiac muscle contraction
KO pathway
ko04261   
LinkDB

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