KEGG   PATHWAY: ggo04261
Entry
ggo04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Gorilla gorilla gorilla (western lowland gorilla)
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
ggo04261  Adrenergic signaling in cardiomyocytes
ggo04261

Other DBs
GO: 0001997
Organism
Gorilla gorilla gorilla (western lowland gorilla) [GN:ggo]
Gene
101149664  ADRB1; beta-1 adrenergic receptor [KO:K04141]
101142746  ADRB2; beta-2 adrenergic receptor [KO:K04142]
101132215  neuroendocrine secretory protein 55 [KO:K04632]
109023045  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X10 [KO:K04632]
101125943  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101141389  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101144031  ADCY3; adenylate cyclase type 3 isoform X4 [KO:K08043] [EC:4.6.1.1]
101125890  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
101150181  ADCY5; adenylate cyclase type 5 isoform X2 [KO:K08045] [EC:4.6.1.1]
101139873  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
101126268  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101142672  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101145410  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101139926  BVES; blood vessel epicardial substance isoform X2 [KO:K21108]
101152354  POPDC2; popeye domain-containing protein 2 isoform X4 [KO:K26206]
101139565  POPDC3; popeye domain-containing protein 3 [KO:K26207]
101149331  KCNK2; potassium channel subfamily K member 2 [KO:K04913]
101151469  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
101134260  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101154367  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 isoform X2 [KO:K01539] [EC:7.2.2.13]
101132606  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
101136136  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
101133472  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
101133872  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
101150859  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
101145254  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
101140721  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540]
109023060  uncharacterized protein LOC109023060 isoform X1 [KO:K01538]
101134383  SLC9A1; sodium/hydrogen exchanger 1 isoform X1 [KO:K05742]
101138642  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 isoform X1 [KO:K04926]
101151453  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
101125769  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X6 [KO:K05850] [EC:7.2.2.10]
101129497  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X2 [KO:K05850] [EC:7.2.2.10]
101151836  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
101146683  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
101140086  SLC8A1; sodium/calcium exchanger 1 isoform X2 [KO:K05849]
101148991  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
101133167  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
101149930  SCN5A; sodium channel protein type 5 subunit alpha isoform X1 [KO:K04838]
101151879  SCN7A; LOW QUALITY PROTEIN: sodium channel protein type 7 subunit alpha [KO:K04839]
101135774  SCN1B; sodium channel subunit beta-1 isoform X3 [KO:K04845]
101147774  SCN4B; sodium channel subunit beta-4 isoform X2 [KO:K04848]
101134060  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
101140987  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
101131714  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
101150507  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
109025142  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
101142555  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X2 [KO:K04863]
101141345  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
101137663  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X4 [KO:K04865]
101128490  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858]
101147075  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860]
101153550  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
101125914  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
101134952  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
101145059  CACNG3; voltage-dependent calcium channel gamma-3 subunit isoform X1 [KO:K04868]
109023084  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
101125554  CACNG5; voltage-dependent calcium channel gamma-5 subunit isoform X2 [KO:K04870]
101143008  CACNG6; voltage-dependent calcium channel gamma-6 subunit isoform X1 [KO:K04871]
101142652  CACNG7; voltage-dependent calcium channel gamma-7 subunit isoform X4 [KO:K04872]
101144712  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
101151475  CALML3; calmodulin-like protein 3 [KO:K02183]
101139013  CALM2; calmodulin-2 isoform X1 [KO:K02183]
101149474  CALM1; calmodulin-1 [KO:K02183]
101151113  CALML5; calmodulin-like protein 5 [KO:K02183]
101139397  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
101140627  calmodulin-2-like [KO:K02183]
101134676  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X29 [KO:K04515] [EC:2.7.11.17]
101153594  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101148194  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
101136547  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
101152456  RYR2; ryanodine receptor 2 isoform X1 [KO:K04962]
101125226  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101152519  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
101142397  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101145146  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
101140471  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X2 [KO:K04354]
101135043  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
101129571  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
101132841  PPP2R2D; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
101127833  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
101147502  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
101134784  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
115930163  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta-like [KO:K11583]
115933053  uncharacterized protein LOC115933053 [KO:K11583]
115932828  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta-like [KO:K11583]
101127596  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X7 [KO:K11584]
101131887  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
101134228  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
101143530  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
101140159  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform-like [KO:K11584]
101143438  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
101129953  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
101126723  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
101137001  TNNI3; troponin I, cardiac muscle [KO:K12044]
101151369  TNNT2; troponin T, cardiac muscle isoform X5 [KO:K12045]
101134313  TPM1; tropomyosin alpha-1 chain isoform X11 [KO:K10373]
109024829  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
101150029  TPM3; tropomyosin alpha-3 chain isoform X10 [KO:K09290]
109025964  tropomyosin alpha-3 chain-like [KO:K09290]
101129425  TPM4; tropomyosin alpha-4 chain isoform X5 [KO:K10375]
115934058  tropomyosin alpha-4 chain-like [KO:K10375]
101150071  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
101138909  myosin-6 [KO:K17751]
101143194  myosin-7 [KO:K17751]
101146701  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
101130342  MYL3; myosin light chain 3 isoform X1 [KO:K12749]
101148883  MYL4; myosin light chain 4 [KO:K12750]
101139566  PLN; cardiac phospholamban [KO:K05852]
101140334  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X2 [KO:K05853] [EC:7.2.2.10]
115932652  LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 3-like [KO:K05853] [EC:7.2.2.10]
101141624  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
101124707  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
101141078  AGT; angiotensinogen precursor [KO:K09821]
101128433  AGTR1; type-1 angiotensin II receptor [KO:K04166]
101129696  AGTR2; type-2 angiotensin II receptor [KO:K04167]
101132819  ADRA1A; alpha-1A adrenergic receptor isoform X1 [KO:K04135]
101142001  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
101136863  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
101149651  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101140350  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
101153613  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101129357  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
101154323  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
101124828  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101140838  PPP1R1A; protein phosphatase 1 regulatory subunit 1A [KO:K08050]
101140164  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101135988  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101152851  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
101144410  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X4 [KO:K05870]
101135003  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
101139584  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101128609  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
101144135  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101144628  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101152081  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
101153965  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
101146740  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X2 [KO:K09049]
101147522  CREM; cAMP-responsive element modulator isoform X6 [KO:K09052]
101136123  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101153785  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X3 [KO:K08014]
101151388  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
101134492  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
101134843  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101148438  MAPK13; mitogen-activated protein kinase 13 isoform X3 [KO:K04441] [EC:2.7.11.24]
101152640  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101125616  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
101154597  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101153738  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
101128463  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
101128094  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
101137723  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101138019  AKT3; 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
ggo04020  Calcium signaling pathway
ggo04151  PI3K-Akt signaling pathway
ggo04260  Cardiac muscle contraction
KO pathway
ko04261   
LinkDB

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