Entry |
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Name |
Adrenergic signaling in cardiomyocytes - Rousettus aegyptiacus (Egyptian rousette)
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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.
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Class |
Organismal Systems; Circulatory system
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Pathway map |
ray04261 | Adrenergic signaling in cardiomyocytes |

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Other DBs |
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Organism |
Rousettus aegyptiacus (Egyptian rousette) [GN: ray]
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Gene |
107500067 | GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632] |
107509410 | ATP1B3; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540] |
107512755 | ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540] |
107515690 | ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540] |
107505043 | FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538] |
107503177 | KCNQ1; LOW QUALITY PROTEIN: potassium voltage-gated channel subfamily KQT member 1 [KO:K04926] |
107520362 | potassium voltage-gated channel subfamily E member 1-like [KO:K04894] |
107521052 | SCN7A; LOW QUALITY PROTEIN: sodium channel protein type 7 subunit alpha [KO:K04839] |
107500540 | CACNA1C; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850] |
107516535 | CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851] |
107514999 | CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853] |
107513628 | CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857] |
107520701 | CACNB1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862] |
107513663 | CACNB2; voltage-dependent L-type calcium channel subunit beta-2 isoform X1 [KO:K04863] |
107514227 | CACNB3; voltage-dependent L-type calcium channel subunit beta-3 isoform X1 [KO:K04864] |
107513916 | CACNB4; voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865] |
107501281 | CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858] |
107513293 | CACNA2D2; LOW QUALITY PROTEIN: voltage-dependent calcium channel subunit alpha-2/delta-2 [KO:K04859] |
107516533 | CACNA2D3; LOW QUALITY PROTEIN: voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860] |
107500543 | CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861] |
107510248 | CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866] |
107519239 | CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867] |
107508836 | CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868] |
107510310 | CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869] |
107510308 | CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870] |
107503034 | CACNG6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871] |
107503063 | CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872] |
107503036 | CACNG8; LOW QUALITY PROTEIN: voltage-dependent calcium channel gamma-8 subunit [KO:K04873] |
107510894 | CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17] |
107512385 | CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17] |
107497167 | CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17] |
107498266 | CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17] |
107506800 | PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16] |
107521184 | PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456] |
107500417 | PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456] |
107519027 | PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354] |
107515450 | PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354] |
107500870 | PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354] |
107514412 | PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583] |
107505863 | PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583] |
107508495 | PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583] |
107509328 | PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584] |
107517041 | PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584] |
107521366 | PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584] |
107521621 | PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584] |
107501966 | PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584] |
107513248 | MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351] |
107505691 | ADRA1D; LOW QUALITY PROTEIN: alpha-1D adrenergic receptor [KO:K04137] |
107517194 | GNAQ; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634] |
107506114 | PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11] |
107519930 | PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11] |
107497081 | PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11] |
107514464 | PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11] |
107521072 | PPP1R1A; protein phosphatase 1 regulatory subunit 1A isoform X1 [KO:K08050] |
107505169 | CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870] |
107504977 | ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450] |
107500816 | ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374] |
107509179 | CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048] |
107502779 | CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048] |
107511864 | CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048] |
107510647 | CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048] |
107499057 | CREB3L2; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048] |
107505683 | CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047] |
107498439 | ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049] |
107499884 | RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014] |
107505164 | RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351] |
107516134 | GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630] |
107518173 | GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630] |
107513376 | GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630] |
107511488 | PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153] |
107515658 | PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290] |
107515659 | PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290] |
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Compound |
C01245 | D-myo-Inositol 1,4,5-trisphosphate |
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Reference |
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Authors |
Grimm M, Brown JH |
Title |
Beta-adrenergic receptor signaling in the heart: role of CaMKII. |
Journal |
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Reference |
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Authors |
Yang JH, Saucerman JJ |
Title |
Computational models reduce complexity and accelerate insight into cardiac signaling networks. |
Journal |
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Reference |
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Authors |
Schaub MC, Hefti MA, Zaugg M |
Title |
Integration of calcium with the signaling network in cardiac myocytes. |
Journal |
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Reference |
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Authors |
Taggart P, Boyett MR, Logantha S, Lambiase PD |
Title |
Anger, emotion, and arrhythmias: from brain to heart. |
Journal |
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Reference |
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Authors |
Bers DM |
Title |
Calcium cycling and signaling in cardiac myocytes. |
Journal |
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Reference |
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Authors |
Soltis AR, Saucerman JJ |
Title |
Synergy between CaMKII substrates and beta-adrenergic signaling in regulation of cardiac myocyte Ca(2+) handling. |
Journal |
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Reference |
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Authors |
Wallukat G |
Title |
The beta-adrenergic receptors. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Xiao RP, Cheng H, Zhou YY, Kuschel M, Lakatta EG |
Title |
Recent advances in cardiac beta(2)-adrenergic signal transduction. |
Journal |
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Reference |
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Authors |
Zheng M, Zhu W, Han Q, Xiao RP |
Title |
Emerging concepts and therapeutic implications of beta-adrenergic receptor subtype signaling. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Bers DM |
Title |
Cardiac excitation-contraction coupling. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Saucerman JJ, McCulloch AD |
Title |
Mechanistic systems models of cell signaling networks: a case study of myocyte adrenergic regulation. |
Journal |
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Reference |
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Authors |
Yano M, Ikeda Y, Matsuzaki M |
Title |
Altered intracellular Ca2+ handling in heart failure. |
Journal |
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Reference |
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Authors |
Wehrens XH, Marks AR |
Title |
Novel therapeutic approaches for heart failure by normalizing calcium cycling. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Barry SP, Davidson SM, Townsend PA |
Title |
Molecular regulation of cardiac hypertrophy. |
Journal |
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Related pathway |
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KO pathway |
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LinkDB |
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