KEGG   PATHWAY: btax04261
Entry
btax04261                   Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Budorcas taxicolor (takin)
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
btax04261  Adrenergic signaling in cardiomyocytes
btax04261

Other DBs
GO: 0001997
Organism
Budorcas taxicolor (takin) [GN:btax]
Gene
128043545  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
128043555  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
128043585  RAPGEF4; rap guanine nucleotide exchange factor 4 [KO:K04351]
128043941  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
128043958  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
128044333  [KO:K01539] [EC:7.2.2.13]
128044334  [KO:K01539] [EC:7.2.2.13]
128044413  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
128044416  MYL3; myosin light chain 3 [KO:K12749]
128044429  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
128044465  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
128044759  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
128044903  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
128046449  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
128046532  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
128046584  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
128046666  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 [KO:K04858]
128046735  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
128046764  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
128047085  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
128047111  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
128047350  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
128047362  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
128047426  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
128047602  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
128047663  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
128047773  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha [KO:K11583]
128047885  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
128047959  PPP1R1A; protein phosphatase 1 regulatory subunit 1A isoform X1 [KO:K08050]
128048064  RYR2; ryanodine receptor 2 [KO:K04962]
128048068  [KO:K09290]
128048256  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
128048310  ATP2B1; plasma membrane calcium-transporting ATPase 1 [KO:K05850] [EC:7.2.2.10]
128048317  AGT; angiotensinogen [KO:K09821]
128048350  [KO:K04374]
128048391  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
128048584  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
128048751  AGTR1; type-1 angiotensin II receptor [KO:K04166]
128048899  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
128048945  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
128049033  RAPGEF3; rap guanine nucleotide exchange factor 3 [KO:K08014]
128049472  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
128049625  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
128050312  [KO:K09290]
128050339  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
128050399  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
128050904  ADRB2; beta-2 adrenergic receptor [KO:K04142]
128051169  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
128051297  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
128051408  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
128051508  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
128051757  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
128052002  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
128052044  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
128052214  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
128052307  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
128052479  TPM2; tropomyosin beta chain [KO:K10374]
128052693  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
128053254  POPDC3; popeye domain-containing protein 3 [KO:K26207]
128053563  BVES; blood vessel epicardial substance [KO:K21108]
128053757  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
128053851  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
128053854  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
128053855  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
128054050  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
128054194  [KO:K17751]
128054195  [KO:K17751]
128054209  TPM1; tropomyosin alpha-1 chain isoform X1 [KO:K10373]
128054267  CALM1; calmodulin-1 [KO:K02183]
128054423  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
128054609  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
128054614  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
128054644  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
128055125  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
128055294  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
128055801  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
128055912  SLC8A1; sodium/calcium exchanger 1 [KO:K05849]
128056208  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
128056429  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
128056529  ATP2B2; plasma membrane calcium-transporting ATPase 2 [KO:K05850] [EC:7.2.2.10]
128056684  CALM2; calmodulin-2 [KO:K02183]
128056879  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
128057155  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
128057268  SCN5A; sodium channel protein type 5 subunit alpha [KO:K04838]
128057390  POPDC2; popeye domain-containing protein 2 isoform X1 [KO:K26206]
128058011  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
128058156  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 [KO:K04863]
128058184  [KO:K10375]
128058230  [KO:K02183]
128058250  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
128058303  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
128058642  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
128058829  [KO:K04632]
128058864  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
128059256  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
128060340  SCN4B; sodium channel subunit beta-4 [KO:K04848]
128060385  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
128060694  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
128061157  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
128061188  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
128061193  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
128061238  TNNT2; troponin T, cardiac muscle [KO:K12045]
128061269  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
128061475  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
128061491  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128061581  ATP2B4; plasma membrane calcium-transporting ATPase 4 [KO:K05850] [EC:7.2.2.10]
128061611  KCNK2; potassium channel subfamily K member 2 [KO:K04913]
128061892  [KO:K05850] [EC:7.2.2.10]
128062068  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1 [KO:K05853] [EC:7.2.2.10]
128062159  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform isoform X1 [KO:K10351]
128062160  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
128062181  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
128063025  CACNG6; voltage-dependent calcium channel gamma-6 subunit isoform X1 [KO:K04871]
128063102  SCN1B; sodium channel subunit beta-1 [KO:K04845]
128063240  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
128063310  TNNI3; troponin I, cardiac muscle [KO:K12044]
128063396  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
128063523  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
128063641  SLC9A1; sodium/hydrogen exchanger 1 isoform X1 [KO:K05742]
128063702  CACNG8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
128063783  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
128063810  CALM3; calmodulin-3 [KO:K02183]
128063870  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128063966  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
128064089  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 [KO:K04865]
128064592  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
128065119  MYL4; myosin light chain 4 [KO:K12750]
128065125  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
128065234  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
128065237  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 [KO:K04862]
128065366  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
128065383  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
128065393  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
128065398  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
128065610  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
128065652  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
128066123  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
128066367  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
128066441  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
128066723  [KO:K11583]
128067048  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128067358  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
128067499  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
128067781  PPP2R2D; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
128067997  ADRB1; beta-1 adrenergic receptor [KO:K04141]
128068193  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
128068474  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
128068503  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
128068545  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
128068898  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
128069702  ATP2B3; plasma membrane calcium-transporting ATPase 3 [KO:K05850] [EC:7.2.2.10]
128069887  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
128069911  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
128070004  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
128070222  [KO:K03456]
128070224  [KO:K03456]
128070433  AGTR2; type-2 angiotensin II receptor [KO:K04167]
128071103  [KO:K05870]
128071502  SCN7A; sodium channel protein type 7 subunit alpha [KO:K04839]
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
btax04020  Calcium signaling pathway
btax04151  PI3K-Akt signaling pathway
btax04260  Cardiac muscle contraction
KO pathway
ko04261   

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