KEGG   PATHWAY: pmei04371
Entry
pmei04371                   Pathway                                
Name
Apelin signaling pathway - Poecilia mexicana (shortfin molly)
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
pmei04371  Apelin signaling pathway
pmei04371

Other DBs
GO: 0060183
Organism
Poecilia mexicana (shortfin molly) [GN:pmei]
Gene
106903786  mef2b; myocyte-specific enhancer factor 2B [KO:K09261]
106904308  prkce; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
106904663  [KO:K05858] [EC:3.1.4.11]
106904740  [KO:K04537]
106904769  [KO:K07826]
106904799  [KO:K02183]
106904980  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
106905004  [KO:K09262]
106905100  prkag3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
106905108  [KO:K04963]
106905118  [KO:K21289] [EC:2.7.1.153]
106905188  [KO:K08048] [EC:4.6.1.1]
106905790  [KO:K04639]
106905872  [KO:K04962]
106906069  [KO:K08046] [EC:4.6.1.1]
106906084  [KO:K12750]
106906182  [KO:K05689]
106906228  [KO:K04345] [EC:2.7.11.11]
106906316  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
106906561  [KO:K07199]
106906981  [KO:K04371] [EC:2.7.11.24]
106907075  [KO:K04547]
106907484  [KO:K04674] [EC:2.7.11.30]
106907646  becn1; beclin-1 isoform X1 [KO:K08334]
106908051  [KO:K04958]
106908205  [KO:K18050] [EC:2.7.11.13]
106908272  [KO:K05689]
106908316  [KO:K04543]
106908435  [KO:K05689]
106909201  map1lc3a; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
106909302  [KO:K04501]
106909348  [KO:K04500]
106909541  [KO:K04718] [EC:2.7.1.91]
106909547  [KO:K05689]
106909548  [KO:K05689]
106909666  [KO:K05849]
106909743  [KO:K04688] [EC:2.7.11.1]
106909751  [KO:K04174]
106910050  [KO:K04174]
106910053  pik3cg; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
106910104  [KO:K08048] [EC:4.6.1.1]
106910254  [KO:K08046] [EC:4.6.1.1]
106910448  [KO:K12313]
106911059  pik3r4; phosphoinositide 3-kinase regulatory subunit 4 isoform X1 [KO:K08333] [EC:2.7.11.1]
106911171  [KO:K07830]
106911618  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
106911661  [KO:K07200]
106911877  [KO:K07830]
106912005  [KO:K00907] [EC:2.7.11.18]
106912093  [KO:K07830]
106912248  gng10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
106912408  [KO:K05689]
106912436  [KO:K04634]
106912827  [KO:K07830]
106913919  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
106913936  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
106913966  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
106914059  [KO:K04962]
106914248  myl3; myosin light chain 3 [KO:K12749]
106914417  [KO:K00907] [EC:2.7.11.18]
106914433  [KO:K08041] [EC:4.6.1.1]
106914539  [KO:K04718] [EC:2.7.1.91]
106914774  klf2; Krueppel-like factor 2 [KO:K17845]
106914900  jag1; protein jagged-1 [KO:K06052]
106914961  [KO:K08046] [EC:4.6.1.1]
106915289  apln; apelin [KO:K05225]
106915624  mef2a; myocyte-specific enhancer factor 2A isoform X1 [KO:K09260]
106915654  [KO:K20995]
106915777  [KO:K08049] [EC:4.6.1.1]
106915816  map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
106916041  kras; GTPase KRas isoform X1 [KO:K07827]
106916046  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
106916097  mylk; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
106916316  [KO:K04536]
106916336  [KO:K04630]
106916615  slc9a1; sodium/hydrogen exchanger 1 isoform X1 [KO:K05742]
106916681  gnb5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
106916842  lipe; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
106917273  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
106917342  hras; GTPase HRas [KO:K02833]
106917460  [KO:K05849]
106917560  [KO:K04542]
106918490  [KO:K04630]
106918514  [KO:K04630]
106918686  [KO:K04961]
106918970  sphk1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
106919288  rps6; 40S ribosomal protein S6 [KO:K02991]
106919449  nos1; nitric oxide synthase, brain isoform X1 [KO:K13240] [EC:1.14.13.39]
106919496  [KO:K04688] [EC:2.7.11.1]
106919502  [KO:K04549]
106919524  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
106919797  [KO:K07200]
106919898  [KO:K07825]
106919952  mef2d; myocyte-specific enhancer factor 2D isoform X1 [KO:K09262]
106920133  [KO:K04347]
106920259  [KO:K00907] [EC:2.7.11.18]
106920589  adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
106920699  hdac4; histone deacetylase 4 isoform X1 [KO:K11406] [EC:3.5.1.98]
106920816  [KO:K08043] [EC:4.6.1.1]
106921081  [KO:K04174]
106921104  calml4; calmodulin-like protein 4 [KO:K02183]
106921617  prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
106921707  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
106921722  gng8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
106921753  [KO:K04961]
106921759  plat; tissue-type plasminogen activator isoform X1 [KO:K01343] [EC:3.4.21.68]
106921995  nrf1; nuclear respiratory factor 1 isoform X1 [KO:K11831]
106922021  sphk2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
106922027  [KO:K08049] [EC:4.6.1.1]
106922057  prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
106922305  [KO:K09203]
106922556  pik3r6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
106922561  pik3r5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
106922633  [KO:K08042] [EC:4.6.1.1]
106922637  [KO:K05849]
106922665  gng3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
106922942  [KO:K02183]
106922974  map1lc3c; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
106923107  [KO:K04501]
106923200  ctgf; connective tissue growth factor [KO:K06827]
106923514  [KO:K04501]
106923528  [KO:K05742]
106923625  [KO:K04345] [EC:2.7.11.11]
106923653  [KO:K07188] [EC:3.1.1.79]
106923694  map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
106923979  [KO:K04548]
106924337  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
106924430  serpine1; plasminogen activator inhibitor 1 [KO:K03982]
106924508  [KO:K04634]
106924536  [KO:K04542]
106924741  slc8a3; sodium/calcium exchanger 3 [KO:K05849]
106924785  [KO:K23605]
106924888  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
106924954  [KO:K11406] [EC:3.5.1.98]
106925495  [KO:K04174]
106925846  adcy5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
106925857  mef2c; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454]
106925933  [KO:K08041] [EC:4.6.1.1]
106926028  [KO:K04454]
106926166  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
106926215  mras; ras-related protein M-Ras [KO:K07831]
106926353  [KO:K04630]
106926488  [KO:K05849]
106926677  apela; apelin receptor early endogenous ligand [KO:K25355]
106926785  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
106926897  [KO:K08042] [EC:4.6.1.1]
106927092  [KO:K05869] [EC:2.7.11.17]
106927223  tfam; transcription factor A, mitochondrial [KO:K11830]
106927233  [KO:K06052]
106927276  [KO:K04630]
106927339  [KO:K08047] [EC:4.6.1.1]
106927347  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
106927524  [KO:K04456] [EC:2.7.11.1]
106927814  [KO:K10351]
106927904  [KO:K07199]
106927928  gnb3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
106928688  [KO:K04688] [EC:2.7.11.1]
106928752  [KO:K21290]
106928777  adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
106928955  [KO:K04639]
106929278  [KO:K05849]
106929282  [KO:K05858] [EC:3.1.4.11]
106929696  [KO:K00907] [EC:2.7.11.18]
106929997  gng5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
106929999  gnb4; guanine nucleotide-binding protein subunit beta-4 isoform X1 [KO:K04538]
106930009  [KO:K04345] [EC:2.7.11.11]
106930214  [KO:K04542]
106930332  gng4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
106930373  slc8a2; sodium/calcium exchanger 2 [KO:K05849]
106930404  [KO:K10435]
106930415  calm2; calmodulin [KO:K02183]
106930500  [KO:K04500]
106930605  egr1; early growth response protein 1 [KO:K09203]
106930732  ryr3; ryanodine receptor 3 isoform X1 [KO:K04963]
106930936  [KO:K04347]
106930974  [KO:K07200]
106931018  [KO:K04345] [EC:2.7.11.11]
106931036  [KO:K00907] [EC:2.7.11.18]
106931194  [KO:K07827]
106931433  [KO:K10351]
106931485  hdac5; histone deacetylase 5 isoform X1 [KO:K11406] [EC:3.5.1.98]
106931586  agtr1; type-1 angiotensin II receptor [KO:K04166]
106931834  smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
106931922  [KO:K10351]
106932106  [KO:K04456] [EC:2.7.11.1]
106932178  pik3c3; phosphatidylinositol 3-kinase catalytic subunit type 3 [KO:K00914] [EC:2.7.1.137]
106932289  itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
106932415  [KO:K04539]
106932947  [KO:K04547]
106933362  [KO:K04542]
106933433  gng12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
106933633  [KO:K04456] [EC:2.7.11.1]
106933653  itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
106933946  [KO:K08049] [EC:4.6.1.1]
106934105  mtor; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
106934170  wdr86; WD repeat-containing protein 86 [KO:K04536]
106934245  calm3; calmodulin [KO:K02183]
106934247  [KO:K21289] [EC:2.7.1.153]
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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
pmei04010  MAPK signaling pathway
pmei04020  Calcium signaling pathway
pmei04140  Autophagy - animal
pmei04150  mTOR signaling pathway
pmei04270  Vascular smooth muscle contraction
pmei04530  Tight junction
KO pathway
ko04371   

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