KEGG   PATHWAY: pleu04261
Entry
pleu04261                   Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Peromyscus leucopus (white-footed mouse)
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
pleu04261  Adrenergic signaling in cardiomyocytes
pleu04261

Other DBs
GO: 0001997
Organism
Peromyscus leucopus (white-footed mouse) [GN:pleu]
Gene
114680674  Plcb3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
114681418  Calm3; calmodulin-3 [KO:K02183]
114681419  Slc8a2; sodium/calcium exchanger 2 [KO:K05849]
114681524  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114682025  [KO:K04632]
114682029  [KO:K04632]
114682088  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
114682187  Agtr2; type-2 angiotensin II receptor [KO:K04167]
114682227  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
114682497  Scn5a; LOW QUALITY PROTEIN: sodium channel protein type 5 subunit alpha [KO:K04838]
114682732  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114683042  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
114683299  Cacna1s; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
114683665  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
114683953  [KO:K06269] [EC:3.1.3.16]
114684152  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
114685054  Ryr2; LOW QUALITY PROTEIN: ryanodine receptor 2 [KO:K04962]
114685348  Atp1a3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
114685849  [KO:K10375]
114685987  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
114686117  Slc8a1; LOW QUALITY PROTEIN: sodium/calcium exchanger 1 [KO:K05849]
114686204  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
114686251  Agtr1; type-1 angiotensin II receptor [KO:K04166]
114686672  Atp2a1; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
114686858  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
114687046  Bves; blood vessel epicardial substance [KO:K21108]
114687048  Popdc3; popeye domain-containing protein 3 [KO:K26207]
114687192  Ppp2r5a; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
114687339  Cacna2d1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X3 [KO:K04858]
114687520  Cacng8; voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
114687522  Cacng7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
114687528  Cacng6; voltage-dependent calcium channel gamma-6 subunit isoform X1 [KO:K04871]
114687991  [KO:K04374]
114688126  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
114689064  [KO:K11583]
114689156  Tnni3; troponin I, cardiac muscle [KO:K12044]
114689622  Atp2b2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
114689726  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
114689830  Adra1b; alpha-1B adrenergic receptor [KO:K04136]
114689941  Atp1b1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
114690258  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X2 [KO:K03456]
114690437  Cacng4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
114690438  Cacng5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
114690439  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
114690478  Cacng1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
114690660  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114690690  Atp1a2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
114690694  [KO:K01539] [EC:7.2.2.13]
114690974  Atp1b3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
114690977  Tpm1; tropomyosin alpha-1 chain isoform X1 [KO:K10373]
114691010  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
114691197  Scn4b; sodium channel subunit beta-4 [KO:K04848]
114691201  [KO:K01538]
114691640  Calml4; calmodulin-like protein 4 isoform X2 [KO:K02183]
114692206  Cacng3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
114692344  Scn7a; LOW QUALITY PROTEIN: sodium channel protein type 7 subunit alpha [KO:K04839]
114693019  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
114693020  Mapk11; mitogen-activated protein kinase 11 isoform X5 [KO:K04441] [EC:2.7.11.24]
114693042  Ppp2r2d; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
114693143  Pik3r5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
114693144  Pik3r6; phosphoinositide 3-kinase regulatory subunit 6 isoform X2 [KO:K21290]
114693172  Atp1b2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
114693374  Ppp2r3c; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
114693540  Ppp2r3a; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
114693931  Cacnb2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
114693962  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
114693978  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X7 [KO:K04515] [EC:2.7.11.17]
114694084  [KO:K05853] [EC:7.2.2.10]
114694160  Kcnq1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
114694218  Cacng2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
114694285  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
114696121  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
114696284  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
114696600  Ppp1r1a; protein phosphatase 1 regulatory subunit 1A isoform X1 [KO:K08050]
114696911  [KO:K04634]
114697069  Adrb1; beta-1 adrenergic receptor [KO:K04141]
114697107  Adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
114697505  Actc1; actin, alpha cardiac muscle 1 [KO:K12314]
114697724  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
114698097  Atp2b4; LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 4 [KO:K05850] [EC:7.2.2.10]
114698133  Tnnt2; troponin T, cardiac muscle [KO:K12045]
114698218  Kcnk2; potassium channel subfamily K member 2 isoform X1 [KO:K04913]
114698264  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
114698419  Kcne1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
114698446  Cacnb4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
114698498  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
114698572  Atp1a1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
114698733  Slc8a3; LOW QUALITY PROTEIN: sodium/calcium exchanger 3 [KO:K05849]
114698927  Scn1b; sodium channel subunit beta-1 [KO:K04845]
114699520  Adra1d; alpha-1D adrenergic receptor [KO:K04137]
114699702  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
114699988  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
114700207  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
114700759  Cacna2d4; voltage-dependent calcium channel subunit alpha-2/delta-4 isoform X1 [KO:K04861]
114700762  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X8 [KO:K04850]
114700827  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
114701075  [KO:K04166]
114701199  Atp2b1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
114701281  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
114701485  Popdc2; LOW QUALITY PROTEIN: popeye domain-containing protein 2 [KO:K26206]
114701602  Ppp2r2b; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X3 [KO:K04354]
114702071  Ppp2r2c; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
114702139  Cacna2d3; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860]
114702283  Myl4; myosin light chain 4 [KO:K12750]
114702318  [KO:K05850] [EC:7.2.2.10]
114702710  [KO:K04135]
114702810  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
114703046  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114703087  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
114703207  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
114703209  Tpm2; tropomyosin beta chain isoform X4 [KO:K10374]
114703666  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858] [EC:3.1.4.11]
114703672  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
114704332  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114704477  Rapgef4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
114704560  Atp2a2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
114704570  Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
114704572  [KO:K10351]
114704841  Adcy5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
114705020  Calm1; calmodulin-1 [KO:K02183]
114705023  Rps6ka5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
114705057  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
114705242  Myl3; myosin light chain 3 [KO:K12749]
114705315  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
114705847  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
114705921  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
114705938  Slc9a1; sodium/hydrogen exchanger 1 [KO:K05742]
114706162  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
114706165  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
114706243  Atp2b3; plasma membrane calcium-transporting ATPase 3 isoform X2 [KO:K05850] [EC:7.2.2.10]
114706333  Atp2a3; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
114706913  Cacnb1; voltage-dependent L-type calcium channel subunit beta-1 isoform X3 [KO:K04862]
114707150  Agt; angiotensinogen [KO:K09821]
114707299  Adra1a; LOW QUALITY PROTEIN: alpha-1A adrenergic receptor [KO:K04135]
114707321  Ppp2r2a; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
114707380  Adrb2; beta-2 adrenergic receptor [KO:K04142]
114707396  Camk2a; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
114707877  Tpm3; tropomyosin alpha-3 chain isoform X12 [KO:K09290]
114707907  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
114708193  Tnnc1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
114708228  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
114708260  Calml6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
114708453  Pik3cg; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
114708501  Adcy7; LOW QUALITY PROTEIN: adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
114708522  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
114708536  Cacnb3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
114708554  Rapgef3; rap guanine nucleotide exchange factor 3 [KO:K08014]
114708688  [KO:K17751]
114708693  [KO:K17751]
114708701  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
114708768  [KO:K02183]
114708779  Calml3; calmodulin-like protein 3 [KO:K02183]
114709209  Calm2; calmodulin-2 [KO:K02183]
114709571  Tpm4; tropomyosin alpha-4 chain isoform X2 [KO:K10375]
114709764  Atp1b4; protein ATP1B4 isoform X1 [KO:K01540]
114710523  [KO:K04371] [EC:2.7.11.24]
114710615  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
114710697  Pln; cardiac phospholamban [KO:K05852]
114710954  Cacna2d2; LOW QUALITY PROTEIN: voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
114710969  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
119087871  [KO:K04962]
119087872  [KO:K04962]
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
pleu04020  Calcium signaling pathway
pleu04151  PI3K-Akt signaling pathway
pleu04260  Cardiac muscle contraction
KO pathway
ko04261   

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