KEGG   PATHWAY: mdo04261
Entry
mdo04261                    Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Monodelphis domestica (gray short-tailed opossum)
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
mdo04261  Adrenergic signaling in cardiomyocytes
mdo04261

Other DBs
GO: 0001997
Organism
Monodelphis domestica (gray short-tailed opossum) [GN:mdo]
Gene
100027410  ADRB1; adrenoceptor beta 1 [KO:K04141]
100031542  ADRB2; adrenoceptor beta 2 [KO:K04142]
100021523  GNAS; GNAS complex locus [KO:K04632]
100029582  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
100030463  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
100013164  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
100025332  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
100030872  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
100019274  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
100013823  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
100026554  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
100013831  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
100028158  BVES; blood vessel epicardial substance [KO:K21108]
100016472  POPDC2; popeye domain containing 2 [KO:K26206]
100619108  POPDC3; popeye domain containing 3 [KO:K26207]
100023531  KCNK2; potassium two pore domain channel subfamily K member 2 [KO:K04913]
100011211  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
100026861  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100032298  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100029759  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
100029754  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
100015422  ATP1B2; ATPase Na+/K+ transporting subunit beta 2 [KO:K01540]
100020118  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
100019139  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
100618619  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
107652422  FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
100017140  SLC9A1; solute carrier family 9 member A1 [KO:K05742]
100033066  uncharacterized LOC100033066 [KO:K04926]
100025694  KCNE1; potassium voltage-gated channel subfamily E regulatory subunit 1 [KO:K04894]
100011221  ATP2B1; ATPase plasma membrane Ca2+ transporting 1 [KO:K05850] [EC:7.2.2.10]
100024542  ATP2B2; ATPase plasma membrane Ca2+ transporting 2 [KO:K05850] [EC:7.2.2.10]
100014855  ATP2B3; ATPase plasma membrane Ca2+ transporting 3 [KO:K05850] [EC:7.2.2.10]
100016381  ATP2B4; ATPase plasma membrane Ca2+ transporting 4 [KO:K05850] [EC:7.2.2.10]
100033060  plasma membrane calcium-transporting ATPase 1-like [KO:K05850] [EC:7.2.2.10]
100020329  SLC8A2; solute carrier family 8 member A2 [KO:K05849]
100010180  SLC8A1; solute carrier family 8 member A1 [KO:K05849]
100020311  SLC8A3; solute carrier family 8 member A3 [KO:K05849]
100653514  SCN5A; sodium voltage-gated channel alpha subunit 5 [KO:K04838]
100616839  SCN1B; sodium voltage-gated channel beta subunit 1 [KO:K04845]
100031519  SCN4B; sodium voltage-gated channel beta subunit 4 [KO:K04848]
100021421  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
100014450  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
100019531  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
100013684  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
100017883  CACNB1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04862]
100020184  CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863]
100016894  CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864]
100019993  CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865]
100012746  CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858]
100028700  CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859]
100013859  CACNA2D3; calcium voltage-gated channel auxiliary subunit alpha2delta 3 [KO:K04860]
100021296  CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861]
100024738  CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866]
100025020  CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867]
100013388  CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868]
100024718  CACNG4; calcium voltage-gated channel auxiliary subunit gamma 4 [KO:K04869]
100029175  voltage-dependent calcium channel gamma-6 subunit-like [KO:K04871]
100009868  voltage-dependent calcium channel gamma-7 subunit-like [KO:K04872]
100021688  CALM3; calmodulin 3 [KO:K02183]
100018191  CALM1; calmodulin 1 [KO:K02183]
100032171  CALM2; calmodulin 2 [KO:K02183]
100025795  CALML4; calmodulin like 4 [KO:K02183]
100015722  calmodulin-alpha-like [KO:K02183]
100022649  calmodulin-alpha-like [KO:K02183]
100011784  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
100010898  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
100024521  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
100028973  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
100028207  RYR2; ryanodine receptor 2 [KO:K04962]
100012652  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
100017519  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
100026516  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
100028805  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
100023749  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
100014202  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
100018121  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
100023958  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
100011289  PPP2R3B; protein phosphatase 2 regulatory subunit B''beta [KO:K11583]
100011688  PPP2R3C; protein phosphatase 2 regulatory subunit B''gamma [KO:K11583]
100016573  PPP2R3A; protein phosphatase 2 regulatory subunit B''alpha [KO:K11583]
100017824  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
100010758  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
100022186  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
100016488  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
100031298  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
100019898  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
100029055  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
100020553  TNNC1; troponin C1, slow skeletal and cardiac type [KO:K05865]
100032908  TNNI3; troponin I3, cardiac type [KO:K12044]
100013928  TNNT2; troponin T2, cardiac type [KO:K12045]
100016737  TPM1; tropomyosin 1 (alpha) [KO:K10373]
100020343  TPM2; tropomyosin 2 (beta) [KO:K10374]
100015402  TPM3; tropomyosin 3 [KO:K09290]
100617065  TPM4; tropomyosin 4 [KO:K10375]
100026925  ACTC1; actin, alpha, cardiac muscle 1 [KO:K12314]
100024758  MYH7; myosin heavy chain 7 [KO:K17751]
100030608  MYH6; myosin heavy chain 6 [KO:K17751]
100019715  MYL2; myosin light chain 2 [KO:K10351]
100018980  MYL3; myosin light chain 3 [KO:K12749]
100021133  MYL4; myosin light chain 4 [KO:K12750]
100617747  PLN; phospholamban [KO:K05852]
100014945  ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:7.2.2.10]
100619889  sarcoplasmic/endoplasmic reticulum calcium ATPase 3-like [KO:K05853] [EC:7.2.2.10]
100015597  ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:7.2.2.10]
103098393  sarcoplasmic/endoplasmic reticulum calcium ATPase 3-like [KO:K05853] [EC:7.2.2.10]
100029465  AGT; angiotensinogen [KO:K09821]
100017858  AGTR1; angiotensin II receptor type 1 [KO:K04166]
100010566  AGTR2; angiotensin II receptor type 2 [KO:K04167]
100017802  ADRA1A; adrenoceptor alpha 1A [KO:K04135]
100025515  ADRA1B; adrenoceptor alpha 1B [KO:K04136]
100030860  ADRA1D; adrenoceptor alpha 1D [KO:K04137]
100011605  GNAQ; G protein subunit alpha q [KO:K04634]
100033281  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
100031660  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
100031869  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
100031263  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
100024674  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
100028096  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100012916  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100017874  RPS6KA5; ribosomal protein S6 kinase A5 [KO:K04445] [EC:2.7.11.1]
100014049  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
100025939  ATF2; activating transcription factor 2 [KO:K04450]
100012224  ATF4; activating transcription factor 4 [KO:K04374]
100017208  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
100020067  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
100022547  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
100015046  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
103104366  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
100032634  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
100025603  ATF6B; activating transcription factor 6 beta [KO:K09049]
100018119  CREM; cAMP responsive element modulator [KO:K09052]
100016570  BCL2; BCL2, apoptosis regulator [KO:K02161]
100025283  RAPGEF4; Rap guanine nucleotide exchange factor 4 [KO:K04351]
100010279  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100010891  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100026324  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
100028821  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100013052  GNAI1; G protein subunit alpha i1 [KO:K04630]
100030095  GNAI3; G protein subunit alpha i3 [KO:K04630]
100032986  GNAI2; G protein subunit alpha i2 [KO:K04630]
100009879  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
100012464  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
100014564  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
100019947  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
100027373  AKT3; AKT serine/threonine kinase 3 [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
mdo04020  Calcium signaling pathway
mdo04151  PI3K-Akt signaling pathway
mdo04260  Cardiac muscle contraction
KO pathway
ko04261   
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