KEGG   PATHWAY: gga04261
gga04261                    Pathway                                

Adrenergic signaling in cardiomyocytes - Gallus gallus (chicken)
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
gga04261  Adrenergic signaling in cardiomyocytes

Other DBs
GO: 0001997
Gallus gallus (chicken) [GN:gga]
101750705  ADRB1; beta-1 adrenergic receptor [KO:K04141]
427623  ADRB2; beta-2 adrenergic receptor [KO:K04142]
419313  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
420788  ADCY1; adenylate cyclase type 1 isoform X2 [KO:K08041] [EC:]
420935  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:]
422013  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:]
395340  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:]
107050028  adenylate cyclase type 6 [KO:K08046] [EC:]
415732  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:]
420328  ADCY8; adenylate cyclase type 8 isoform X2 [KO:K08048] [EC:]
395339  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:]
424542  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X7 [KO:K04345] [EC:]
396530  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 precursor [KO:K01539] [EC:]
422365  ATP1B4; protein ATP1B4 [KO:K01540]
396529  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
396549  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
107050378  sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
419770  FXYD2; sodium/potassium-transporting ATPase subunit gamma [KO:K01538]
419580  SLC9A1; sodium/hydrogen exchanger 1 precursor [KO:K05742]
423090  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 isoform X1 [KO:K04926]
101748386  KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894]
419934  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X2 [KO:K05850] [EC:]
374244  ATP2B1; plasma membrane calcium-transporting ATPase 1 [KO:K05850] [EC:]
415958  ATP2B2; plasma membrane calcium-transporting ATPase 2 [KO:K05850] [EC:]
395759  SLC8A3; sodium/calcium exchanger 3 precursor [KO:K05849]
395760  SLC8A1; sodium/calcium exchanger 1 precursor [KO:K05849]
107057643  SLC8A2; sodium/calcium exchanger 2 [KO:K05849]
395947  SCN5A; sodium channel protein type 5 subunit alpha [KO:K04838]
107051305  sodium channel subunit beta-1 [KO:K04845]
419774  SCN4B; sodium channel subunit beta-4 isoform X1 [KO:K04848]
395891  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
395895  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
395985  CATSPER2; voltage-dependent L-type calcium channel subunit alpha-1S isoform 1 [KO:K04857]
777366  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
428420  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863]
107050029  voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864]
374259  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform a [KO:K04865]
768444  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 preproprotein [KO:K04858]
430150  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859]
415996  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X2 [KO:K04860]
100858946  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
417428  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
427909  CACNG2; voltage-dependent calcium channel gamma-2 subunit isoform X2 [KO:K04867]
395378  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
373924  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
417429  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
107050634  CACNG7; LOW QUALITY PROTEIN: voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
396523  CALM1; neo-calmodulin [KO:K02183]
416692  CALML3; calmodulin, striated muscle [KO:K02183]
395855  CALM2; calmodulin [KO:K02183]
427515  CALML4; calmodulin-like protein 4 [KO:K02183]
374174  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:]
374175  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:]
423737  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:]
422688  CAMK2D; calcium/calmodulin-dependent protein kinase type II delta chain [KO:K04515] [EC:]
421508  RYR2; ryanodine receptor 2 isoform X1 [KO:K04962]
396021  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:]
416318  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:]
422858  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X2 [KO:K04354]
416350  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X2 [KO:K04354]
423970  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
419523  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
418670  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
423324  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X2 [KO:K11583]
424733  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X2 [KO:K11583]
423512  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
423460  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]
421250  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
421372  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
396019  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:]
416872  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:]
100858156  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:]
396032  TNNC1; troponin C, slow skeletal and cardiac muscles [KO:K05865]
396433  TNNT2; troponin T, cardiac muscle isoforms [KO:K12045]
396366  TPM1; tropomyosin alpha-1 chain [KO:K10373]
396430  TPM2; tropomyosin beta chain [KO:K09290]
770103  TPM3; tropomyosin alpha-3 chain isoform a [KO:K09290]
107055375  TPM4; tropomyosin alpha-4 chain isoform X1 [KO:K10375]
423298  ACTC1; actin, alpha cardiac muscle 1 [KO:K12314]
426652  ACTBL2L; actin, alpha skeletal muscle B [KO:K12314]
395350  MYH7; myosin-7 [KO:K17751]
429272  MYO7L2; myosin-7 [KO:K17751]
416874  MYL2; myosin regulatory light chain 2A, cardiac muscle isoform [KO:K10351]
396067  MYL3; myosin light chain 1, cardiac muscle [KO:K12749]
396472  MYL4; myosin light chain, embryonic [KO:K12750]
396378  PLN; cardiac phospholamban [KO:K05852]
395707  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:]
396446  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform 2 [KO:K05853] [EC:]
421543  AGT; angiotensinogen [KO:K09821]
396065  AGTR1; type-1 angiotensin II receptor [KO:K04166]
428708  AGTR2; type-2 angiotensin II receptor [KO:K04167]
428203  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
373890  ADRA1B; alpha-1B adrenergic receptor isoform X1 [KO:K04136]
422933  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
427262  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
423014  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X2 [KO:K05858] [EC:]
416730  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:]
427687  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:]
417430  PRKCA; protein kinase C alpha type [KO:K02677] [EC:]
100857781  PPP1R1A; protein phosphatase 1 regulatory subunit 1A [KO:K08050]
373953  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
423408  RPS6KA5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:]
395099  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
395727  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
395693  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
427417  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
418123  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X2 [KO:K09048]
428333  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100859610  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X2 [KO:K09048]
428435  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X3 [KO:K09047]
378903  CREM; cAMP-responsive element modulator isoform 1 [KO:K09052]
396282  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
426888  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014]
429022  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X4 [KO:K04351]
417739  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:]
421183  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:]
769763  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
771145  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:]
374097  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
396367  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
396368  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
417706  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:]
417319  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
769202  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X2 [KO:K21290]
395928  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:]
421497  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
101750560  RAC-beta serine/threonine-protein kinase [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)
gga04020  Calcium signaling pathway
gga04260  Cardiac muscle contraction
KO pathway

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