KEGG   PATHWAY: amj04371
Entry
amj04371                    Pathway                                
Name
Apelin signaling pathway - Alligator mississippiensis (American alligator)
Description
Apelin is an endogenous peptide capable of binding the apelin receptor (APJ), which was originally described as an orphan G-protein-coupled receptor. Apelin and APJ are widely expressed in various tissues and organ systems. They are implicated in different key physiological processes such as angiogenesis, cardiovascular functions, cell proliferation and energy metabolism regulation. On the other hand, this ligand receptor couple is also involved in several pathologies including diabetes, obesity, cardiovascular disease and cancer.
Class
Environmental Information Processing; Signal transduction
Pathway map
amj04371  Apelin signaling pathway
amj04371

Other DBs
GO: 0060183
Organism
Alligator mississippiensis (American alligator) [GN:amj]
Gene
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]
102575865  ADCY10; adenylate cyclase 10, soluble [KO:K11265] [EC:4.6.1.1]
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]
102571969  LIPE; lipase E, hormone sensitive type [KO:K07188] [EC:3.1.1.79]
102571164  APLN; apelin [KO:K05225]
106738485  APELA; apelin receptor early endogenous ligand [KO:K25355]
102563117  APLNR; apelin receptor [KO:K04174]
102565041  apelin receptor A [KO:K04174]
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]
102568881  GNB1; G protein subunit beta 1 [KO:K04536]
106736636  GNB3; G protein subunit beta 3 [KO:K07825]
102577024  GNB4; G protein subunit beta 4 [KO:K04538]
106737105  GNB5; G protein subunit beta 5 [KO:K04539]
102573196  GNG2; G protein subunit gamma 2 [KO:K07826]
102562582  GNG3; G protein subunit gamma 3 [KO:K04540]
102561211  GNG4; G protein subunit gamma 4 [KO:K04541]
102559752  GNG5; G protein subunit gamma 5 [KO:K04542]
102569715  GNG7; G protein subunit gamma 7 [KO:K04543]
106739241  GNG8; G protein subunit gamma 8 [KO:K04544]
102572832  GNG10; G protein subunit gamma 10 [KO:K04545]
102568360  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
102574789  GNG12; G protein subunit gamma 12 [KO:K04347]
102563301  GNG13; G protein subunit gamma 13 [KO:K04547]
102576658  GNGT2; G protein subunit gamma transducin 2 [KO:K04549]
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]
102561752  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102570264  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102567087  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102563585  RYR1; ryanodine receptor 1 [KO:K04961]
102572051  RYR2; ryanodine receptor 2 [KO:K04962]
102564536  RYR3; ryanodine receptor 3 [KO:K04963]
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]
102561243  NOS1; nitric oxide synthase 1 [KO:K13240] [EC:1.14.13.39]
106737013  NOS2; nitric oxide synthase 2 [KO:K13241] [EC:1.14.13.39]
102575253  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
102576791  PRKCE; protein kinase C epsilon [KO:K18050] [EC:2.7.11.13]
102575554  SLC9A1; solute carrier family 9 member A1 [KO:K05742]
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]
102557905  myosin light chain kinase, smooth muscle [KO:K00907] [EC:2.7.11.18]
102561520  MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
102568638  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
102574082  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
102563829  MYL2; myosin light chain 2 [KO:K10351]
102565509  MYL3; myosin light chain 3 [KO:K12749]
102571199  MYL4; myosin light chain 4 [KO:K12750]
102562157  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102574430  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102575936  GTPase HRas [KO:K07827]
102566357  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102573349  RRAS2; related RAS viral (r-ras) oncogene homolog 2 [KO:K07830]
102560726  RRAS; related RAS viral (r-ras) oncogene homolog [KO:K07830]
102573274  MRAS; muscle RAS oncogene homolog [KO:K07831]
102576986  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102563228  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
106736997  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
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]
106736874  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
102571014  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
102562280  RPS6; ribosomal protein S6 [KO:K02991]
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]
102574334  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
102566924  EGR1; early growth response 1 [KO:K09203]
102569137  SPP1; secreted phosphoprotein 1 [KO:K06250]
102572438  JAG1; jagged 1 [KO:K06052]
102573730  neurogenic locus notch homolog protein 3-like [KO:K20995]
102563714  CCND1; cyclin D1 [KO:K04503]
102562481  PDE3B; phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
102577320  PIK3C3; phosphatidylinositol 3-kinase catalytic subunit type 3 [KO:K00914] [EC:2.7.1.137]
102569602  PIK3R4; phosphoinositide-3-kinase regulatory subunit 4 [KO:K08333] [EC:2.7.11.1]
102565076  BECN1; beclin 1 [KO:K08334]
102574281  MAP1LC3A; microtubule associated protein 1 light chain 3 alpha [KO:K10435]
102563937  microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
102566159  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
102576264  MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435]
102576537  MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435]
102576605  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.31]
102570371  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.31]
102560973  PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
102568469  PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
102566003  PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
102574506  PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
102560751  5'-AMP-activated protein kinase subunit gamma-3-like [KO:K07200]
102558908  PLIN1; perilipin 1 [KO:K08768]
102576297  PPARGC1A; PPARG coactivator 1 alpha [KO:K07202]
102564498  NRF1; nuclear respiratory factor 1 [KO:K11831]
102558790  TFAM; transcription factor A, mitochondrial [KO:K11830]
102561449  KLF2; Kruppel like factor 2 [KO:K17845]
102558563  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
102566845  SPHK2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
102568562  GNA13; G protein subunit alpha 13 [KO:K04639]
102571105  calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
102566359  CAMK4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
102568102  HDAC5; histone deacetylase 5 [KO:K11406] [EC:3.5.1.98]
102576843  HDAC4; histone deacetylase 4 [KO:K11406] [EC:3.5.1.98]
102576485  MEF2A; myocyte enhancer factor 2A [KO:K09260]
102562261  MEF2B; myocyte-specific enhancer factor 2B [KO:K09261]
102573957  MEF2C; myocyte enhancer factor 2C [KO:K04454]
102557713  MEF2D; myocyte enhancer factor 2D [KO:K09262]
102568992  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
102564903  SMAD2; SMAD family member 2 [KO:K04500]
102564680  SMAD3; SMAD family member 3 [KO:K23605]
102572775  mothers against decapentaplegic homolog 4 [KO:K04501]
102576984  SMAD4; SMAD family member 4 [KO:K04501]
102577392  ACTA2; actin, alpha 2, smooth muscle, aorta [KO:K12313]
106737158  CDH1; cadherin 1 [KO:K05689]
102576711  B-cadherin-like [KO:K05689]
102577158  CTGFB; connective tissue growth factor [KO:K06827]
102559952  CTGF; connective tissue growth factor [KO:K06827]
102569750  AGTR1; angiotensin II receptor type 1 [KO:K04166]
102563594  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
102560959  PLAT; plasminogen activator, tissue type [KO:K01343] [EC:3.4.21.68]
Compound
C00076  Calcium cation
C00080  H+
C00165  Diacylglycerol
C00290  Fibrin
C00533  Nitric oxide
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C06124  Sphingosine 1-phosphate
Reference
PMID:26143239
  Authors
Yang P, Maguire JJ, Davenport AP
  Title
Apelin, Elabela/Toddler, and biased agonists as novel therapeutic agents in the cardiovascular system.
  Journal
Trends Pharmacol Sci 36:560-7 (2015)
DOI:10.1016/j.tips.2015.06.002
Reference
PMID:22140623
  Authors
Andersen CU, Hilberg O, Mellemkjaer S, Nielsen-Kudsk JE, Simonsen U
  Title
Apelin and pulmonary hypertension.
  Journal
Pulm Circ 1:334-46 (2011)
DOI:10.4103/2045-8932.87299
Reference
PMID:25275559
  Authors
Chapman NA, Dupre DJ, Rainey JK
  Title
The apelin receptor: physiology, pathology, cell signalling, and ligand modulation of a peptide-activated class A GPCR.
  Journal
Biochem Cell Biol 92:431-40 (2014)
DOI:10.1139/bcb-2014-0072
Reference
PMID:18272138
  Authors
Japp AG, Newby DE
  Title
The apelin-APJ system in heart failure: pathophysiologic relevance and therapeutic potential.
  Journal
Biochem Pharmacol 75:1882-92 (2008)
DOI:10.1016/j.bcp.2007.12.015
Reference
PMID:25652330
  Authors
Folino A, Montarolo PG, Samaja M, Rastaldo R
  Title
Effects of apelin on the cardiovascular system.
  Journal
Heart Fail Rev 20:505-18 (2015)
DOI:10.1007/s10741-015-9475-x
Reference
PMID:23943882
  Authors
O'Carroll AM, Lolait SJ, Harris LE, Pope GR
  Title
The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis.
  Journal
J Endocrinol 219:R13-35 (2013)
DOI:10.1530/JOE-13-0227
Reference
PMID:23973488
  Authors
Liu QF, Yu HW, You L, Liu MX, Li KY, Tao GZ
  Title
Apelin-13-induced proliferation and migration induced of rat vascular smooth muscle cells is mediated by the upregulation of Egr-1.
  Journal
Biochem Biophys Res Commun 439:235-40 (2013)
DOI:10.1016/j.bbrc.2013.08.051
Reference
PMID:26254105
  Authors
Novakova V, Sandhu GS, Dragomir-Daescu D, Klabusay M
  Title
Apelinergic system in endothelial cells and its role in angiogenesis in myocardial ischemia.
  Journal
Vascul Pharmacol 76:1-10 (2016)
DOI:10.1016/j.vph.2015.08.005
Reference
PMID:21725702
  Authors
Castan-Laurell I, Dray C, Attane C, Duparc T, Knauf C, Valet P
  Title
Apelin, diabetes, and obesity.
  Journal
Endocrine 40:1-9 (2011)
DOI:10.1007/s12020-011-9507-9
Reference
PMID:23924696
  Authors
Li L, Li L, Xie F, Zhang Z, Guo Y, Tang G, Lv D, Lu Q, Chen L, Li J
  Title
Jagged-1/Notch3 signaling transduction pathway is involved in apelin-13-induced vascular smooth muscle cells proliferation.
  Journal
Acta Biochim Biophys Sin (Shanghai) 45:875-81 (2013)
DOI:10.1093/abbs/gmt085
Reference
PMID:24990699
  Authors
Wu D, He L, Chen L
  Title
Apelin/APJ system: a promising therapy target for hypertension.
  Journal
Mol Biol Rep 41:6691-703 (2014)
DOI:10.1007/s11033-014-3552-4
Reference
PMID:20539939
  Authors
Liu C, Su T, Li F, Li L, Qin X, Pan W, Feng F, Chen F, Liao D, Chen L
  Title
PI3K/Akt signaling transduction pathway is involved in rat vascular smooth muscle cell proliferation induced by apelin-13.
  Journal
Acta Biochim Biophys Sin (Shanghai) 42:396-402 (2010)
DOI:10.1093/abbs/gmq035
Reference
PMID:26607438
  Authors
Xie F, Liu W, Feng F, Li X, He L, Lv D, Qin X, Li L, Li L, Chen L
  Title
Apelin-13 promotes cardiomyocyte hypertrophy via PI3K-Akt-ERK1/2-p70S6K and PI3K-induced autophagy.
  Journal
Acta Biochim Biophys Sin (Shanghai) 47:969-80 (2015)
DOI:10.1093/abbs/gmv111
Reference
PMID:27979574
  Authors
Lu L, Wu D, Li L, Chen L
  Title
Apelin/APJ system: A bifunctional target for cardiac hypertrophy.
  Journal
Int J Cardiol 230:164-170 (2017)
DOI:10.1016/j.ijcard.2016.11.215
Reference
PMID:16182514
  Authors
Carmen GY, Victor SM
  Title
Signalling mechanisms regulating lipolysis.
  Journal
Cell Signal 18:401-8 (2006)
DOI:10.1016/j.cellsig.2005.08.009
Reference
PMID:27650065
  Authors
Hu H, He L, Li L, Chen L
  Title
Apelin/APJ system as a therapeutic target in diabetes and its complications.
  Journal
Mol Genet Metab 119:20-7 (2016)
DOI:10.1016/j.ymgme.2016.07.012
Reference
PMID:25914650
  Authors
Bertrand C, Valet P, Castan-Laurell I
  Title
Apelin and energy metabolism.
  Journal
Front Physiol 6:115 (2015)
DOI:10.3389/fphys.2015.00115
Reference
PMID:26385179
  Authors
Yao F, Lv YC, Zhang M, Xie W, Tan YL, Gong D, Cheng HP, Liu D, Li L, Liu XY, Zheng XL, Tang CK
  Title
Apelin-13 impedes foam cell formation by activating Class III PI3K/Beclin-1-mediated autophagic pathway.
  Journal
Biochem Biophys Res Commun 466:637-43 (2015)
DOI:10.1016/j.bbrc.2015.09.045
Reference
PMID:22842084
  Authors
Than A, Cheng Y, Foh LC, Leow MK, Lim SC, Chuah YJ, Kang Y, Chen P
  Title
Apelin inhibits adipogenesis and lipolysis through distinct molecular pathways.
  Journal
Mol Cell Endocrinol 362:227-41 (2012)
DOI:10.1016/j.mce.2012.07.002
Reference
PMID:24055369
  Authors
Yu XH, Tang ZB, Liu LJ, Qian H, Tang SL, Zhang DW, Tian GP, Tang CK
  Title
Apelin and its receptor APJ in cardiovascular diseases.
  Journal
Clin Chim Acta 428:1-8 (2014)
DOI:10.1016/j.cca.2013.09.001
Reference
PMID:25931124
  Authors
Than A, He HL, Chua SH, Xu D, Sun L, Leow MK, Chen P
  Title
Apelin Enhances Brown Adipogenesis and Browning of White Adipocytes.
  Journal
J Biol Chem 290:14679-91 (2015)
DOI:10.1074/jbc.M115.643817
Reference
PMID:25139773
  Authors
Fu J, Li Z, Zhang H, Mao Y, Wang A, Wang X, Zou Z, Zhang X
  Title
Molecular pathways regulating the formation of brown-like adipocytes in white adipose tissue.
  Journal
Diabetes Metab Res Rev 31:433-52 (2015)
DOI:10.1002/dmrr.2600
Reference
PMID:21464822
  Authors
Aharoni-Simon M, Hann-Obercyger M, Pen S, Madar Z, Tirosh O
  Title
Fatty liver is associated with impaired activity of PPARgamma-coactivator 1alpha (PGC1alpha) and mitochondrial biogenesis in mice.
  Journal
Lab Invest 91:1018-28 (2011)
DOI:10.1038/labinvest.2011.55
Reference
PMID:22995518
  Authors
McLean DL, Kim J, Kang Y, Shi H, Atkins GB, Jain MK, Chun HJ
  Title
Apelin/APJ signaling is a critical regulator of statin effects in vascular endothelial cells--brief report.
  Journal
Arterioscler Thromb Vasc Biol 32:2640-3 (2012)
DOI:10.1161/ATVBAHA.112.300317
Reference
PMID:22028387
  Authors
Pchejetski D, Foussal C, Alfarano C, Lairez O, Calise D, Guilbeau-Frugier C, Schaak S, Seguelas MH, Wanecq E, Valet P, Parini A, Kunduzova O
  Title
Apelin prevents cardiac fibroblast activation and collagen production through inhibition of sphingosine kinase 1.
  Journal
Eur Heart J 33:2360-9 (2012)
DOI:10.1093/eurheartj/ehr389
Reference
PMID:26944568
  Authors
Huang S, Chen L, Lu L, Li L
  Title
The apelin-APJ axis: A novel potential therapeutic target for organ fibrosis.
  Journal
Clin Chim Acta 456:81-8 (2016)
DOI:10.1016/j.cca.2016.02.025
Reference
PMID:19093215
  Authors
Liu G, Han J, Profirovic J, Strekalova E, Voyno-Yasenetskaya TA
  Title
Galpha13 regulates MEF2-dependent gene transcription in endothelial cells: role in angiogenesis.
  Journal
Angiogenesis 12:1-15 (2009)
DOI:10.1007/s10456-008-9123-3
Reference
PMID:23603510
  Authors
Kang Y, Kim J, Anderson JP, Wu J, Gleim SR, Kundu RK, McLean DL, Kim JD, Park H, Jin SW, Hwa J, Quertermous T, Chun HJ
  Title
Apelin-APJ signaling is a critical regulator of endothelial MEF2 activation in cardiovascular development.
  Journal
Circ Res 113:22-31 (2013)
DOI:10.1161/CIRCRESAHA.113.301324
Reference
PMID:25164121
  Authors
Wang LY, Diao ZL, Zhang DL, Zheng JF, Zhang QD, Ding JX, Liu WH
  Title
The regulatory peptide apelin: a novel inhibitor of renal interstitial fibrosis.
  Journal
Amino Acids 46:2693-704 (2014)
DOI:10.1007/s00726-014-1826-8
Reference
PMID:26756969
  Authors
Zhou Y, Deng L, Zhao D, Chen L, Yao Z, Guo X, Liu X, Lv L, Leng B, Xu W, Qiao G, Shan H
  Title
MicroRNA-503 promotes angiotensin II-induced cardiac fibrosis by targeting Apelin-13.
  Journal
J Cell Mol Med 20:495-505 (2016)
DOI:10.1111/jcmm.12754
Reference
PMID:27825851
  Authors
Zhong JC, Zhang ZZ, Wang W, McKinnie SM, Vederas JC, Oudit GY
  Title
Targeting the apelin pathway as a novel therapeutic approach for cardiovascular diseases.
  Journal
Biochim Biophys Acta 1863:1942-1950 (2017)
DOI:10.1016/j.bbadis.2016.11.007
Related
pathway
amj04010  MAPK signaling pathway
amj04020  Calcium signaling pathway
amj04140  Autophagy - animal
amj04150  mTOR signaling pathway
amj04270  Vascular smooth muscle contraction
amj04530  Tight junction
KO pathway
ko04371   
LinkDB

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