KEGG   PATHWAY: leri04261
Entry
leri04261                   Pathway                                
Name
Adrenergic signaling in cardiomyocytes - Leucoraja erinacea (little skate)
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
leri04261  Adrenergic signaling in cardiomyocytes
leri04261

Other DBs
GO: 0001997
Organism
Leucoraja erinacea (little skate) [GN:leri]
Gene
129713251  beta-1 adrenergic receptor-like [KO:K04141]
129704037  adrb1; LOW QUALITY PROTEIN: beta-1 adrenergic receptor [KO:K04141]
129701665  beta-2 adrenergic receptor-like [KO:K04142]
129707193  gnas; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
129710284  adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
129705029  adcy7; adenylate cyclase type 7 isoform X1 [KO:K08042] [EC:4.6.1.1]
129711549  LOW QUALITY PROTEIN: adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
129699833  LOW QUALITY PROTEIN: adenylate cyclase type 3-like [KO:K08043] [EC:4.6.1.1]
129699122  adcy5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
129696342  adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
129699829  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
129706900  adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
129702540  popdc2; popeye domain-containing 2 isoform X1 [KO:K26206]
129699721  kcnk2a; potassium channel subfamily K member 2 isoform X1 [KO:K04913]
129700701  LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit beta-like [KO:K04345] [EC:2.7.11.11]
129714364  LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
129702739  sodium/potassium-transporting ATPase subunit alpha [KO:K01539] [EC:7.2.2.13]
129708748  sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
129702332  protein ATP1B4-like isoform X1 [KO:K01540]
129702733  sodium/potassium-transporting ATPase subunit beta-1-like [KO:K01540]
129703307  atp1b3a; sodium/potassium-transporting ATPase subunit beta-3a [KO:K01540]
129694010  sodium/potassium-transporting ATPase subunit beta-2-like isoform X1 [KO:K01540]
129709792  slc9a1a; sodium/hydrogen exchanger 1 isoform X1 [KO:K05742]
129705854  potassium voltage-gated channel subfamily KQT member 1-like [KO:K04926]
129706523  kcnq1.2; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
129708921  plasma membrane calcium-transporting ATPase 1-like [KO:K05850] [EC:7.2.2.10]
129706360  plasma membrane calcium-transporting ATPase 1-like isoform X1 [KO:K05850] [EC:7.2.2.10]
129704867  atp2b2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
129694711  LOW QUALITY PROTEIN: sodium/calcium exchanger 1-like [KO:K05849]
129700381  slc8a3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
129714263  sodium/calcium exchanger 3-like [KO:K05849]
129715842  sodium/calcium exchanger 1-like [KO:K05849]
129714255  LOW QUALITY PROTEIN: sodium channel protein type 4 subunit alpha-like [KO:K04838]
129706126  cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
129704437  voltage-dependent L-type calcium channel subunit alpha-1D-like isoform X1 [KO:K04851]
129708776  voltage-dependent L-type calcium channel subunit alpha-1S-like isoform X1 [KO:K04857]
129710085  cacnb1; voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
129707610  voltage-dependent L-type calcium channel subunit beta-2-like isoform X1 [KO:K04863]
129699085  cacnb4a; voltage-dependent L-type calcium channel subunit beta-4a isoform X1 [KO:K04865]
129707784  voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858]
129704613  cacna2d2a; voltage-dependent calcium channel subunit alpha-2/delta-2a isoform X1 [KO:K04859]
129704444  cacna2d3a; voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860]
129706539  cacna2d4a; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
129708165  voltage-dependent calcium channel gamma-1 subunit-like [KO:K04866]
129713811  voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
129706861  voltage-dependent calcium channel gamma-3 subunit-like isoform X1 [KO:K04868]
129708164  cacng4b; calcium channel, voltage-dependent, gamma subunit 4b [KO:K04869]
129708163  voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
129699639  calm2b; calmodulin 2b, (phosphorylase kinase, delta) [KO:K02183]
129700047  calm1a; calmodulin-1a [KO:K02183]
129711692  calglandulin-like [KO:K02183]
129712743  calmodulin-like protein 4 [KO:K02183]
129701572  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
129713199  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
129700367  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
129712893  camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
129699873  ryr2a; ryanodine receptor 2 [KO:K04962]
129701798  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
129701049  ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
129712339  ppp2r1ba; protein phosphatase 2, regulatory subunit A, beta a [KO:K03456]
129716089  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like [KO:K03456]
129701422  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
129713307  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
129701676  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
129703940  ppp2r2d; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
129697824  ppp2r3b; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
129703585  ppp2r3a; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
129700226  ppp2r3c; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
129697575  ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
129699740  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
129699953  ppp2r5eb; protein phosphatase 2, regulatory subunit B', epsilon isoform X1 [KO:K11584]
129700546  ppp2r5ca; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
129709421  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit A [KO:K06269] [EC:3.1.3.16]
129697622  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
129693451  serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
129704884  troponin C, slow skeletal and cardiac muscles [KO:K05865]
129708533  troponin T, cardiac muscle-like [KO:K12045]
129713584  tpm1; tropomyosin alpha-1 chain isoform X1 [KO:K10373]
129695715  tropomyosin alpha-4 chain-like isoform X1 [KO:K09290]
129716190  LOW QUALITY PROTEIN: tropomyosin alpha-3 chain-like [KO:K09290]
129711219  tropomyosin alpha-1 chain isoform X1 [KO:K10375]
129703278  uncharacterized protein LOC129703278 [KO:K12314]
129700313  actin, alpha cardiac muscle 1 [KO:K12314]
129715185  actin, alpha cardiac muscle 1-like [KO:K12314]
129709423  myosin regulatory light chain 2, ventricular/cardiac muscle isoform isoform X1 [KO:K10351]
129714856  myosin light chain 1, cardiac muscle-like [KO:K12749]
129710247  myl4; myosin light chain 4 [KO:K12750]
129697310  pln; cardiac phospholamban [KO:K05852]
129709409  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
129710673  atp2a3; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
129696957  angiotensinogen-like [KO:K09821]
129703332  agtr1a; type-1 angiotensin II receptor [KO:K04166]
129701998  type-2 angiotensin II receptor-like [KO:K04167]
129713305  adra1aa; adrenoceptor alpha 1Aa [KO:K04135]
129701623  alpha-1B adrenergic receptor-like [KO:K04136]
129703199  alpha-1A adrenergic receptor-like [KO:K04137]
129695757  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
129711338  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
129711340  guanine nucleotide-binding protein subunit alpha-11-like [KO:K04634]
129699284  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
129699288  LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
129700502  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2-like [KO:K05858] [EC:3.1.4.11]
129715851  LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
129708162  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
129709053  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129699782  ribosomal protein S6 kinase alpha-5-like [KO:K04445] [EC:2.7.11.1]
129700049  rps6ka5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:2.7.11.1]
129698910  cyclic AMP-responsive element-binding protein 1-like isoform X1 [KO:K05870]
129698729  atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
129713924  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
129695682  creb3l3l; cAMP responsive element binding protein 3-like 3 like [KO:K09048]
129705869  creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
129706242  creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
129711244  cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
129711928  creb5b; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
129716415  atf6b; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
129715369  cAMP-responsive element modulator-like isoform X1 [KO:K09052]
129711578  bcl2b; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129698745  rapgef4a; rap guanine nucleotide exchange factor 4 [KO:K04351]
129707782  mapk12a; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
129707783  mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
129704781  zgc:171775; STKc_p38 domain-containing protein [KO:K04441] [EC:2.7.11.24]
129708685  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
129708686  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
129708880  guanine nucleotide-binding protein G(i) subunit alpha-3-like [KO:K04630]
129707792  gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
129693758  guanine nucleotide-binding protein G(i) subunit alpha-1-like [KO:K04630]
129704748  guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
129704660  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform-like [KO:K21289] [EC:2.7.1.153]
129708408  pik3cg; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
129708084  pik3r5; LOW QUALITY PROTEIN: phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
129708147  phosphoinositide 3-kinase regulatory subunit 6-like [KO:K21290]
129699479  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
129714205  LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase-like [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
leri04020  Calcium signaling pathway
leri04260  Cardiac muscle contraction
KO pathway
ko04261   
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