KEGG   PATHWAY: amj04261
Entry
amj04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Alligator mississippiensis (American alligator)
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
amj04261  Adrenergic signaling in cardiomyocytes
amj04261

Other DBs
GO: 0001997
Organism
Alligator mississippiensis (American alligator) [GN:amj]
Gene
102574660  ADRB1; adrenoceptor beta 1 [KO:K04141]
102567188  ADRB2; adrenoceptor beta 2 [KO:K04142]
102563836  GNAS; GNAS complex locus [KO:K04632]
102573818  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
102562034  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
102566746  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
102558956  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
102562224  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102573402  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102566330  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102562540  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102574362  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102570572  BVES; blood vessel epicardial substance [KO:K21108]
102567122  POPDC2; popeye domain containing 2 [KO:K26206]
102576820  KCNK2; potassium two pore domain channel subfamily K member 2 [KO:K04913]
102572143  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
106737076  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
106737151  sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
102575084  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
102567591  ATP1A1; ATPase Na+/K+ transporting subunit alpha 1 [KO:K01539] [EC:7.2.2.13]
102565782  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
102570388  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
102559077  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
102573901  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
102573878  FXYD2; sodium/potassium-transporting ATPase subunit gamma [KO:K01538]
102575554  SLC9A1; solute carrier family 9 member A1 [KO:K05742]
102563434  KCNQ1; potassium voltage-gated channel subfamily Q member 1 [KO:K04926]
102562053  potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
102559908  KCNE1; potassium voltage-gated channel subfamily E regulatory subunit 1 [KO:K04894]
106736870  plasma membrane calcium-transporting ATPase 2 [KO:K05850] [EC:7.2.2.10]
102574612  ATP2B3; ATPase plasma membrane Ca2+ transporting 3 [KO:K05850] [EC:7.2.2.10]
102566828  ATP2B4; ATPase plasma membrane Ca2+ transporting 4 [KO:K05850] [EC:7.2.2.10]
102564127  ATP2B1; ATPase plasma membrane Ca2+ transporting 1 [KO:K05850] [EC:7.2.2.10]
106737581  sodium/calcium exchanger 2 [KO:K05849]
102575838  SLC8A3; solute carrier family 8 member A3 [KO:K05849]
102573547  SLC8A1; solute carrier family 8 member A1 [KO:K05849]
102565252  sodium channel protein type 5 subunit alpha [KO:K04838]
102568564  SCN1B; sodium voltage-gated channel beta subunit 1 [KO:K04845]
102572946  SCN4B; sodium voltage-gated channel beta subunit 4 [KO:K04848]
102575519  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
102576817  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
102563169  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
102563699  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
102559323  CACNB1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04862]
102559343  CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863]
102559082  CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864]
106736635  CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865]
102565821  CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858]
102558555  CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859]
102570532  CACNA2D3; calcium voltage-gated channel auxiliary subunit alpha2delta 3 [KO:K04860]
106736655  CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861]
102565332  CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866]
102561501  CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867]
102572864  CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868]
102572607  CACNG4; calcium voltage-gated channel auxiliary subunit gamma 4 [KO:K04869]
102572375  CACNG5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870]
102570210  CACNG6; calcium voltage-gated channel auxiliary subunit gamma 6 [KO:K04871]
102569742  CACNG7; calcium voltage-gated channel auxiliary subunit gamma 7 [KO:K04872]
102569980  CACNG8; calcium voltage-gated channel auxiliary subunit gamma 8 [KO:K04873]
102574007  CALM1; calmodulin 1 [KO:K02183]
102573656  CALM2; calmodulin 2 [KO:K02183]
102558596  CALM3; calmodulin [KO:K02183]
102558691  calmodulin-alpha [KO:K02183]
102561470  CALML6; calmodulin like 6 [KO:K02183]
102577125  CALML4; calmodulin like 4 [KO:K02183]
102570318  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
102562159  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
102564631  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
106736808  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
102572051  RYR2; ryanodine receptor 2 [KO:K04962]
102576713  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
102576911  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
102571411  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
102572311  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
102559987  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
102574203  PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
102574435  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
106737028  PPP2R3B; protein phosphatase 2 regulatory subunit B''beta [KO:K11583]
102562834  PPP2R3A; protein phosphatase 2 regulatory subunit B''alpha [KO:K11583]
102559220  PPP2R3C; protein phosphatase 2 regulatory subunit B''gamma [KO:K11583]
102567782  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
106737003  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
102559929  PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
102562888  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
102564365  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
102560817  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
102564750  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
102565419  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
102576773  TNNC1; troponin C1, slow skeletal and cardiac type [KO:K05865]
102575200  TNNI3; troponin I3, cardiac type [KO:K12044]
102568680  TNNT2; troponin T2, cardiac type [KO:K12045]
102562451  TPM1; tropomyosin 1 (alpha) [KO:K10373]
102564090  TPM2; tropomyosin 2 (beta) [KO:K10374]
102557705  TPM3; tropomyosin 3 [KO:K09290]
102563083  TPM4; tropomyosin 4 [KO:K10375]
106736711  ACTC1; actin, alpha, cardiac muscle 1 [KO:K12314]
102570695  actin, aortic smooth muscle [KO:K12314]
102576117  MYH6; myosin-7 [KO:K17751]
102563829  MYL2; myosin light chain 2 [KO:K10351]
102565509  MYL3; myosin light chain 3 [KO:K12749]
102571199  MYL4; myosin light chain 4 [KO:K12750]
102561464  PLN; phospholamban [KO:K05852]
102563916  ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853] [EC:7.2.2.10]
102563371  ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:7.2.2.10]
106736928  ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:7.2.2.10]
102570643  AGT; angiotensinogen [KO:K09821]
102569750  AGTR1; angiotensin II receptor type 1 [KO:K04166]
102565205  AGTR2; angiotensin II receptor type 2 [KO:K04167]
102557676  ADRA1A; adrenoceptor alpha 1A [KO:K04135]
102563347  ADRA1D; adrenoceptor alpha 1D [KO:K04137]
102565550  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102576994  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
102572359  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102566880  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102560430  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102572836  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102564322  PPP1R1A; protein phosphatase 1 regulatory subunit 1A [KO:K08050]
106737342  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102561718  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109282845  mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
102576860  RPS6KA5; ribosomal protein S6 kinase A5 [KO:K04445] [EC:2.7.11.1]
102564978  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
102572172  ATF2; activating transcription factor 2 [KO:K04450]
102564186  ATF4; activating transcription factor 4 [KO:K04374]
102571170  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
102562994  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
102574172  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
102565945  CREB3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
102558288  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
102576266  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
102575911  ATF6B; activating transcription factor 6 beta [KO:K09049]
102572920  CREM; cAMP responsive element modulator [KO:K09052]
102564752  BCL2; BCL2, apoptosis regulator [KO:K02161]
102574517  RAPGEF3; Rap guanine nucleotide exchange factor 3 [KO:K08014]
102568614  RAPGEF4; Rap guanine nucleotide exchange factor 4 [KO:K04351]
102571419  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102571177  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
106736779  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102565670  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
106737098  GNAI2; G protein subunit alpha i2 [KO:K04630]
102571369  GNAI1; G protein subunit alpha i1 [KO:K04630]
102567683  GNAI3; G protein subunit alpha i3 [KO:K04630]
102559272  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
102559047  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
102566809  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
102574794  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102558879  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102564996  AKT1; AKT serine/threonine kinase 1 [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
amj04020  Calcium signaling pathway
amj04260  Cardiac muscle contraction
KO pathway
ko04261   
LinkDB

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