KEGG   PATHWAY: loc04371
Entry
loc04371                    Pathway                                
Name
Apelin signaling pathway - Lepisosteus oculatus (spotted gar)
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
loc04371  Apelin signaling pathway
loc04371

Other DBs
GO: 0060183
Organism
Lepisosteus oculatus (spotted gar) [GN:loc]
Gene
102692556  adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
102696921  adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
102683703  adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
102689480  adcy5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
102693411  adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
102689559  adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
102694194  adenylate cyclase type 8-like isoform X1 [KO:K08048] [EC:4.6.1.1]
102685748  adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
102695743  adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
102694164  adcy10; adenylate cyclase type 10 [KO:K11265] [EC:4.6.1.1]
102688918  prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102686951  prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
107077932  apln; apelin [KO:K05225]
107077049  apela; apelin receptor early endogenous ligand [KO:K25355]
102685279  apelin receptor A-like [KO:K04174]
102690587  guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
102693211  gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
102698552  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
102688414  gnb1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
102699060  gnb3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
102696470  gnb4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
102686407  gnb5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
102682571  gng2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
102693860  gng3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
102693247  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 isoform X1 [KO:K04541]
102688800  gng5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
102685563  gng7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
102689583  gng8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
102693272  gng10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
102694494  guanine nucleotide-binding protein G(T) subunit gamma-T1-like [KO:K04548]
102683202  gngt2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
102686598  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
102682149  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
102691284  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
102682351  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
102694604  itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
102683319  itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102696500  itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
102685847  ryr1; ryanodine receptor 1 [KO:K04961]
102696990  ryr2; ryanodine receptor 2 isoform X1 [KO:K04962]
102687222  ryr3; LOW QUALITY PROTEIN: ryanodine receptor 3 [KO:K04963]
102688560  calm3; calmodulin [KO:K02183]
102688815  calm2; calmodulin [KO:K02183]
102690259  calml4; calmodulin-like protein 4 [KO:K02183]
102695922  calm1; calmodulin [KO:K02183]
102691846  calml6; calmodulin-like protein 6 [KO:K02183]
102699252  nos1; nitric oxide synthase, brain isoform X1 [KO:K13240] [EC:1.14.13.39]
102692649  nos2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
102697373  nitric oxide synthase, endothelial-like [KO:K13242] [EC:1.14.13.39]
102694770  prkce; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
102687426  slc9a1; sodium/hydrogen exchanger 1 isoform X1 [KO:K05742]
102687682  slc8a2; sodium/calcium exchanger 2 [KO:K05849]
102689135  slc8a1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
102686210  slc8a3; sodium/calcium exchanger 3 isoform X2 [KO:K05849]
102694849  sodium/calcium exchanger 3-like [KO:K05849]
102682466  mylk3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
102686027  myosin light chain kinase, smooth muscle-like isoform X1 [KO:K00907] [EC:2.7.11.18]
102685356  mylk2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
102689935  mylk4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
102697050  mylk; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
102682260  myl2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
102683186  myl3; myosin light chain 3 [KO:K12749]
102684478  myl4; myosin light chain 4 [KO:K12750]
102697398  hras; GTPase HRas [KO:K02833]
102696189  kras; GTPase KRas isoform X3 [KO:K07827]
102691327  nras; GTPase NRas [KO:K07828]
102690777  rras2; ras-related protein R-Ras2 [KO:K07830]
102687237  mras; ras-related protein M-Ras [KO:K07831]
102692545  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102691532  map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102686784  map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
102683764  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102695696  rps6kb1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
102691816  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
102686669  rps6; 40S ribosomal protein S6 [KO:K02991]
102699081  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform-like isoform X1 [KO:K21289] [EC:2.7.1.153]
102689190  pik3cg; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X3 [KO:K21289] [EC:2.7.1.153]
102696853  pik3r6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
102697044  pik3r5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
102690433  akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102684446  akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102691207  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102692856  mtor; serine/threonine-protein kinase mTOR isoform X2 [KO:K07203] [EC:2.7.11.1]
102692201  egr1; early growth response protein 1 [KO:K09203]
102683339  jag1; protein jagged-1 [KO:K06052]
102682710  neurogenic locus notch homolog protein 2-like [KO:K20995]
102687804  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
102694452  pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
102689720  pik3c3; phosphatidylinositol 3-kinase catalytic subunit type 3 isoform X1 [KO:K00914] [EC:2.7.1.137]
102682445  pik3r4; phosphoinositide 3-kinase regulatory subunit 4 [KO:K08333] [EC:2.7.11.1]
102687453  becn1; beclin-1 isoform X2 [KO:K08334]
102691899  microtubule-associated proteins 1A/1B light chain 3C-like isoform X2 [KO:K10435]
102692164  map1lc3a; microtubule-associated proteins 1A/1B light chain 3A isoform X1 [KO:K10435]
102686382  map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
102693561  prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X2 [KO:K07198] [EC:2.7.11.31]
102698529  prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
102688739  prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
102687363  5'-AMP-activated protein kinase subunit beta-2-like isoform X1 [KO:K07199]
102683132  prkag3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X2 [KO:K07200]
102683649  prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
102684542  prkag2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
102688233  plin1; perilipin-1 [KO:K08768]
102687278  ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X4 [KO:K07202]
102697624  nrf1; nuclear respiratory factor 1 isoform X2 [KO:K11831]
102686815  tfam; transcription factor A, mitochondrial [KO:K11830]
102696214  klf2; Krueppel-like factor 2 [KO:K17845]
102683742  sphk1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
102687288  gna13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
102698371  calcium/calmodulin-dependent protein kinase type IV-like [KO:K05869] [EC:2.7.11.17]
102690113  camk4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
102692362  hdac5; histone deacetylase 5 isoform X1 [KO:K11406] [EC:3.5.1.98]
102697511  hdac4; histone deacetylase 4 isoform X1 [KO:K11406] [EC:3.5.1.98]
102684314  mef2a; myocyte-specific enhancer factor 2A isoform X7 [KO:K09260]
102683003  mef2b; myocyte-specific enhancer factor 2B [KO:K09261]
102696550  mef2c; myocyte-specific enhancer factor 2C isoform X10 [KO:K04454]
102688747  mef2d; myocyte-specific enhancer factor 2D [KO:K09262]
102688795  tgfbr1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
102689511  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
102692333  smad3; mothers against decapentaplegic homolog 3 isoform X5 [KO:K23605]
102684763  mothers against decapentaplegic homolog 4-like [KO:K04501]
102696431  smad4; LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 4 [KO:K04501]
102682501  acta2; actin, aortic smooth muscle [KO:K12313]
102694645  cadherin-1-like [KO:K05689]
102683213  cdh1; cadherin-1 [KO:K05689]
102697722  ctgf; connective tissue growth factor [KO:K06827]
102682974  connective tissue growth factor-like [KO:K06827]
102696402  agtr1; type-1 angiotensin II receptor [KO:K04166]
102696166  serpine1; plasminogen activator inhibitor 1 [KO:K03982]
102689846  plat; tissue-type plasminogen activator [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
  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
loc04010  MAPK signaling pathway
loc04020  Calcium signaling pathway
loc04140  Autophagy - animal
loc04150  mTOR signaling pathway
loc04270  Vascular smooth muscle contraction
loc04530  Tight junction
KO pathway
ko04371   
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