KEGG   PATHWAY: nni04261
Entry
nni04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Nipponia nippon (crested ibis)
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
nni04261  Adrenergic signaling in cardiomyocytes
nni04261

Other DBs
GO: 0001997
Organism
Nipponia nippon (crested ibis) [GN:nni]
Gene
104022377  ADRB1; beta-1 adrenergic receptor [KO:K04141]
104019019  ADRB2; beta-2 adrenergic receptor [KO:K04142]
104013042  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
104015394  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
104018888  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
104014763  ADCY3; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
104018815  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
104019883  ADCY6; LOW QUALITY PROTEIN: adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
104011289  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
104016868  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
104023465  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
104011137  LOW QUALITY PROTEIN: blood vessel epicardial substance-like [KO:K21108]
104008631  POPDC2; popeye domain-containing protein 2 [KO:K26206]
104019660  KCNK2; potassium channel subfamily K member 2 [KO:K04913]
104015461  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
104008633  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
104012600  ATP1A2; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
104019090  ATP1B4; protein ATP1B4 [KO:K01540]
104016486  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
104014150  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
104008754  FXYD2; sodium/potassium-transporting ATPase subunit gamma [KO:K01538]
104017832  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
104012517  potassium voltage-gated channel subfamily KQT member 1-like [KO:K04926]
104010800  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
104020132  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
104013141  ATP2B4; plasma membrane calcium-transporting ATPase 4 [KO:K05850] [EC:7.2.2.10]
104011641  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
104022940  ATP2B2; LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 2 [KO:K05850] [EC:7.2.2.10]
104022808  sodium/calcium exchanger 2-like [KO:K05849]
104022117  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
104020318  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
104014886  sodium channel protein type 5 subunit alpha-like isoform X1 [KO:K04838]
104014897  LOW QUALITY PROTEIN: sodium channel protein type 5 subunit alpha-like [KO:K04838]
104019056  SCN4B; sodium channel subunit beta-4 [KO:K04848]
104020209  CACNA1C; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
104010825  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
104009116  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F-like [KO:K04851]
104011070  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
104013320  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
104019884  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 [KO:K04864]
104012362  CACNB4; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit beta-4 [KO:K04865]
104010753  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 [KO:K04858]
104008753  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
104015320  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
104020248  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
104014297  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
104021577  CACNG2; voltage-dependent calcium channel gamma-2 subunit isoform X1 [KO:K04867]
104015149  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
104014362  CACNG4; LOW QUALITY PROTEIN: voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
104014296  CACNG5; LOW QUALITY PROTEIN: voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
104010482  CALML3; calmodulin-like protein 3 [KO:K02183]
104017200  CALML4; calmodulin-like protein 4 [KO:K02183]
104011816  calmodulin-like [KO:K02183]
104021521  CALM2; calmodulin [KO:K02183]
104022221  CALM1; LOW QUALITY PROTEIN: calmodulin [KO:K02183]
104022609  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
104016939  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
104014199  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
104019154  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
104011583  RYR2; ryanodine receptor 2 [KO:K04962]
104016606  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
104012002  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
104018039  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
104012034  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
104019519  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
104013866  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
104010618  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
104011781  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
104019305  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
104014507  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
104010131  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
104019671  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
104015794  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
104011867  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
104021492  PPP1CB; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
104020653  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
104008698  TNNC1; troponin C, slow skeletal and cardiac muscles isoform X1 [KO:K05865]
104015333  LOW QUALITY PROTEIN: troponin I, cardiac muscle-like [KO:K12044]
104011082  TNNT2; LOW QUALITY PROTEIN: troponin T, cardiac muscle [KO:K12045]
104015314  tropomyosin alpha-4 chain-like isoform X1 [KO:K10374]
104009105  TPM2; tropomyosin beta chain [KO:K10374]
104011981  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
104018733  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
104009401  actin, alpha skeletal muscle B-like isoform X1 [KO:K12314]
104015900  ACTC1; actin, alpha cardiac muscle 1 isoform X1 [KO:K12314]
104019401  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
104021723  MYL3; myosin light chain 3 [KO:K12749]
104012258  MYL4; myosin light chain 4 [KO:K12750]
104009954  PLN; cardiac phospholamban [KO:K05852]
104019537  ATP2A2; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
104016115  ATP2A3; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
104017811  AGT; angiotensinogen [KO:K09821]
104015689  AGTR1; type-1 angiotensin II receptor [KO:K04166]
104012966  AGTR2; type-2 angiotensin II receptor [KO:K04167]
104019516  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
104016581  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
104018527  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
104020875  GNAQ; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
104022433  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
104022482  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
104020525  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
104014361  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
104011979  PPP1R1A; protein phosphatase 1 regulatory subunit 1A [KO:K08050]
104020099  MAPK1; LOW QUALITY PROTEIN: mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104022234  RPS6KA5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:2.7.11.1]
104010208  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
104010014  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
104021625  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
104015313  LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like [KO:K09048]
104012401  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
104018462  cyclic AMP-responsive element-binding protein 3-like [KO:K09048]
104018284  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
104020372  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
104018808  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
104013914  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
104022258  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
104021857  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
104011982  RAPGEF3; LOW QUALITY PROTEIN: rap guanine nucleotide exchange factor 3 [KO:K08014]
104010004  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
104010702  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
104010773  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
104010338  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
104013235  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
104010747  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
104008688  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
104014537  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
104010725  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
104011006  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
104011017  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
104020263  AKT2; LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104014534  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104011272  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
nni04020  Calcium signaling pathway
nni04260  Cardiac muscle contraction
KO pathway
ko04261   
LinkDB

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