KEGG   PATHWAY: mna04261
mna04261                    Pathway                                

Adrenergic signaling in cardiomyocytes - Miniopterus natalensis
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.
Organismal Systems; Circulatory system
Pathway map
mna04261  Adrenergic signaling in cardiomyocytes

Other DBs
GO: 0001997
Miniopterus natalensis [GN:mna]
107536422  ADRB1; beta-1 adrenergic receptor [KO:K04141]
107540586  ADRB2; beta-2 adrenergic receptor [KO:K04142]
107529329  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
107529353  neuroendocrine secretory protein 55-like [KO:K04632]
107526004  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:]
107540528  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:]
107534062  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:]
107531740  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:]
107527242  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:]
107528232  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:]
107531029  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:]
107539500  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:]
107535777  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:]
107544336  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:]
107543188  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
107545330  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:]
107538456  sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:]
107534181  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:]
107537932  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
107534704  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
107534499  sodium/potassium-transporting ATPase subunit beta-3-like [KO:K01540]
107529056  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
107544529  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
107530783  FXYD2; sodium/potassium-transporting ATPase subunit gamma [KO:K01538]
107540015  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
107539908  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
107541267  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
107538560  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:]
107538818  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:]
107538895  ATP2B1; plasma membrane calcium-transporting ATPase 1 [KO:K05850] [EC:]
107534770  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:]
107541794  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
107536251  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
107540036  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
107524300  SCN5A; sodium channel protein type 5 subunit alpha isoform X1 [KO:K04838]
107527010  SCN7A; sodium channel protein type 7 subunit alpha [KO:K04839]
107543440  SCN1B; sodium channel subunit beta-1 [KO:K04845]
107530808  SCN4B; sodium channel subunit beta-4 [KO:K04848]
107546425  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
107534931  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
107541372  CACNA1F; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
107536018  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
107529017  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 [KO:K04862]
107537293  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
107528234  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
107531651  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
107527170  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 [KO:K04858]
107540175  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859]
107530629  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860]
107546422  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
107531121  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
107545336  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
107544760  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
107530945  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
107538307  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
107540425  CACNG6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871]
107540464  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
107542429  CALML3; calmodulin-like protein 3 [KO:K02183]
107542435  CALML5; calmodulin-like protein 5 [KO:K02183]
107536794  CALM3; calmodulin [KO:K02183]
107540147  CALML6; calmodulin-like protein 6 [KO:K02183]
107544318  CALM2; calmodulin isoform X1 [KO:K02183]
107531584  CALM1; calmodulin [KO:K02183]
107525969  CALML4; calmodulin-like protein 4 [KO:K02183]
107545830  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:]
107542053  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:]
107535228  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:]
107527851  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:]
107542403  ryanodine receptor 2 [KO:K04962]
107527206  ryanodine receptor 2-like [KO:K04962]
107525394  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:]
107534103  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:]
107540441  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
107531299  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
107524098  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
107529884  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
107530370  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
107529477  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
107545227  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
107526093  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
107546091  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
107533585  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
107536901  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
107545671  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
107536493  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
107542012  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
107534692  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:]
107533957  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:]
107529564  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:]
107534791  TNNC1; troponin C, slow skeletal and cardiac muscles isoform X1 [KO:K05865]
107541326  TNNI3; troponin I, cardiac muscle [KO:K12044]
107535978  troponin T, cardiac muscle-like [KO:K12045]
107535979  troponin T, cardiac muscle [KO:K12045]
107533720  TPM1; tropomyosin alpha-1 chain [KO:K10373]
107545025  TPM2; tropomyosin beta chain isoform X1 [KO:K10374]
107543812  TPM3; tropomyosin alpha-3 chain isoform X1 [KO:K09290]
107534317  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
107543021  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
107531658  myosin-7-like [KO:K17751]
107531708  MYH6; myosin-6 isoform X1 [KO:K17751]
107529566  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
107529383  MYL3; myosin light chain 3 [KO:K12749]
107531022  MYL4; myosin light chain 4 [KO:K12750]
107526298  PLN; cardiac phospholamban [KO:K05852]
107529595  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:]
107528003  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:]
107541012  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:]
107524243  AGT; angiotensinogen [KO:K09821]
107544042  AGTR1; type-1 angiotensin II receptor [KO:K04166]
107543671  AGTR2; type-2 angiotensin II receptor [KO:K04167]
107529888  ADRA1A; alpha-1A adrenergic receptor isoform X1 [KO:K04135]
107537855  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
107536281  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
107544926  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107542967  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:]
107536366  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:]
107536369  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:]
107539797  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:]
107538300  PRKCA; protein kinase C alpha type [KO:K02677] [EC:]
107541076  PPP1R1A; protein phosphatase 1 regulatory subunit 1A isoform X1 [KO:K08050]
107541504  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:]
107530451  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
107531586  RPS6KA5; LOW QUALITY PROTEIN: ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:]
107524712  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
107532468  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
107531265  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
107525737  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
107543873  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
107530327  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
107544136  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
107544933  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
107544390  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
107539006  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
107525066  CREM; cAMP-responsive element modulator isoform X1 [KO:K09052]
107545431  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
107528219  RAPGEF3; rap guanine nucleotide exchange factor 3 [KO:K08014]
107531114  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
107545565  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:]
107545613  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:]
107536041  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
107536051  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:]
107545320  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
107540752  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
107545079  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
107530834  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:]
107544506  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
107544531  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
107542383  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:]
107528331  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
107534199  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
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
Grimm M, Brown JH
Beta-adrenergic receptor signaling in the heart: role of CaMKII.
J Mol Cell Cardiol 48:322-30 (2010)
Yang JH, Saucerman JJ
Computational models reduce complexity and accelerate insight into cardiac signaling networks.
Circ Res 108:85-97 (2011)
Schaub MC, Hefti MA, Zaugg M
Integration of calcium with the signaling network in cardiac myocytes.
J Mol Cell Cardiol 41:183-214 (2006)
Taggart P, Boyett MR, Logantha S, Lambiase PD
Anger, emotion, and arrhythmias: from brain to heart.
Front Physiol 2:67 (2011)
Bers DM
Calcium cycling and signaling in cardiac myocytes.
Annu Rev Physiol 70:23-49 (2008)
Soltis AR, Saucerman JJ
Synergy between CaMKII substrates and beta-adrenergic signaling in regulation of cardiac myocyte Ca(2+) handling.
Biophys J 99:2038-47 (2010)
Wallukat G
The beta-adrenergic receptors.
Herz 27:683-90 (2002)
Xiao RP
Beta-adrenergic signaling in the heart: dual coupling of the beta2-adrenergic receptor to G(s) and G(i) proteins.
Sci STKE 2001:re15 (2001)
Xiao RP, Cheng H, Zhou YY, Kuschel M, Lakatta EG
Recent advances in cardiac beta(2)-adrenergic signal transduction.
Circ Res 85:1092-100 (1999)
Zheng M, Zhu W, Han Q, Xiao RP
Emerging concepts and therapeutic implications of beta-adrenergic receptor subtype signaling.
Pharmacol Ther 108:257-68 (2005)
Kuzumoto M, Takeuchi A, Nakai H, Oka C, Noma A, Matsuoka S
Simulation analysis of intracellular Na+ and Cl- homeostasis during beta 1-adrenergic stimulation of cardiac myocyte.
Prog Biophys Mol Biol 96:171-86 (2008)
Bers DM
Cardiac excitation-contraction coupling.
Nature 415:198-205 (2002)
Ho D, Yan L, Iwatsubo K, Vatner DE, Vatner SF
Modulation of beta-adrenergic receptor signaling in heart failure and longevity: targeting adenylyl cyclase type 5.
Heart Fail Rev 15:495-512 (2010)
Saucerman JJ, McCulloch AD
Mechanistic systems models of cell signaling networks: a case study of myocyte adrenergic regulation.
Prog Biophys Mol Biol 85:261-78 (2004)
Yano M, Ikeda Y, Matsuzaki M
Altered intracellular Ca2+ handling in heart failure.
J Clin Invest 115:556-64 (2005)
Wehrens XH, Marks AR
Novel therapeutic approaches for heart failure by normalizing calcium cycling.
Nat Rev Drug Discov 3:565-73 (2004)
Triposkiadis F, Karayannis G, Giamouzis G, Skoularigis J, Louridas G, Butler J
The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications.
J Am Coll Cardiol 54:1747-62 (2009)
Barry SP, Davidson SM, Townsend PA
Molecular regulation of cardiac hypertrophy.
Int J Biochem Cell Biol 40:2023-39 (2008)
mna04020  Calcium signaling pathway
mna04151  PI3K-Akt signaling pathway
mna04260  Cardiac muscle contraction
KO pathway

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