KEGG   PATHWAY: fpg04371
Entry
fpg04371                    Pathway                                
Name
Apelin signaling pathway - Falco peregrinus (peregrine falcon)
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
fpg04371  Apelin signaling pathway
fpg04371

Other DBs
GO: 0060183
Organism
Falco peregrinus (peregrine falcon) [GN:fpg]
Gene
101914769  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
101911647  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
101921567  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
101922323  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
101916278  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
101914615  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
101921528  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
101921768  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
101921803  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
101911454  APLN; apelin [KO:K05225]
101917823  APLNR; apelin receptor [KO:K04174]
101924920  GNAI2; G protein subunit alpha i2 [KO:K04630]
101918521  GNAI3; G protein subunit alpha i3 [KO:K04630]
101917880  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101924451  GNB1; G protein subunit beta 1 [KO:K04536]
101913486  GNB3; G protein subunit beta 3 [KO:K07825]
101911968  GNB4; G protein subunit beta 4 [KO:K04538]
101919047  GNB5; G protein subunit beta 5 [KO:K04539]
101922152  GNG2; G protein subunit gamma 2 [KO:K07826]
101910999  GNG4; G protein subunit gamma 4 [KO:K04541]
101918290  GNG5; G protein subunit gamma 5 [KO:K04542]
101916450  GNG7; G protein subunit gamma 7 [KO:K04543]
101921860  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
101921479  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
101918590  GNG12; G protein subunit gamma 12 [KO:K04347]
101918487  GNG13; G protein subunit gamma 13 [KO:K04547]
101915154  GNGT2; G protein subunit gamma transducin 2 [KO:K04549]
101912464  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101916711  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
101922366  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
101912415  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
101916606  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101920370  inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101911646  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101913442  RYR2; ryanodine receptor 2 [KO:K04962]
101915080  RYR3; ryanodine receptor 3 [KO:K04963]
101923747  calmodulin, striated muscle [KO:K02183]
101916818  CALM2; calmodulin 2 [KO:K02183]
101919099  CALM1; calmodulin 1 [KO:K02183]
101912097  CALML4; calmodulin like 4 [KO:K02183]
101916747  NOS1; nitric oxide synthase 1 [KO:K13240] [EC:1.14.13.39]
101921726  NOS2; nitric oxide synthase 2 [KO:K13241] [EC:1.14.13.39]
101918492  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
101917755  PRKCE; protein kinase C epsilon [KO:K18050] [EC:2.7.11.13]
101911642  SLC9A1; solute carrier family 9 member A1 [KO:K05742]
101919694  SLC8A2; solute carrier family 8 member A2 [KO:K05849]
101913700  SLC8A3; solute carrier family 8 member A3 [KO:K05849]
101922583  SLC8A1; solute carrier family 8 member A1 [KO:K05849]
101910574  myosin light chain kinase, smooth muscle-like [KO:K00907] [EC:2.7.11.18]
101922032  MYLK2; myosin light chain kinase 2 [KO:K00907] [EC:2.7.11.18]
101922066  myosin light chain kinase 3-like [KO:K00907] [EC:2.7.11.18]
101922502  MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
101917440  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
101916533  MYL2; myosin light chain 2 [KO:K10351]
101911020  MYL3; myosin light chain 3 [KO:K12749]
101923465  myosin light chain, embryonic [KO:K12750]
101916982  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
101917762  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
101921486  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
101919417  RRAS2; related RAS viral (r-ras) oncogene homolog 2 [KO:K07830]
101919448  MRAS; muscle RAS oncogene homolog [KO:K07831]
101911761  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
101924998  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101924296  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101914611  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101910744  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
101914136  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
101913222  RPS6; ribosomal protein S6 [KO:K02991]
101910831  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
101916251  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
101916082  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
101910975  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
101918846  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
101918868  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
101919512  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
101915762  EGR1; early growth response 1 [KO:K09203]
101911265  SPP1; secreted phosphoprotein 1 [KO:K06250]
101923066  JAG1; jagged 1 [KO:K06052]
101921282  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
101914937  CCND1; cyclin D1 [KO:K04503]
101919766  PDE3B; phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
101923473  PIK3C3; phosphatidylinositol 3-kinase catalytic subunit type 3 [KO:K00914] [EC:2.7.1.137]
101911885  PIK3R4; phosphoinositide-3-kinase regulatory subunit 4 [KO:K08333] [EC:2.7.11.1]
101918517  BECN1; beclin 1 [KO:K08334]
101913520  DYNLRB1; dynein light chain roadblock-type 1 [KO:K10435]
101910929  MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435]
101924258  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
101912927  MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435]
101919295  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.31]
101913786  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.31]
101918959  PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
101922375  PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
101917527  PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
101921211  PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
101915063  PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
101914393  PLIN1; perilipin 1 [KO:K08768]
101914584  peroxisome proliferator-activated receptor gamma coactivator 1-alpha [KO:K07202]
101922073  NRF1; nuclear respiratory factor 1 [KO:K11831]
101923001  TFAM; transcription factor A, mitochondrial [KO:K11830]
101913685  KLF2; Kruppel like factor 2 [KO:K17845]
106112566  Krueppel-like factor 2 [KO:K17845]
101921272  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
101922831  GNA13; G protein subunit alpha 13 [KO:K04639]
101917352  calcium/calmodulin-dependent protein kinase type IV-like [KO:K05869] [EC:2.7.11.17]
101913113  CAMK4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
101918053  HDAC4; histone deacetylase 4 [KO:K11406] [EC:3.5.1.98]
101914331  HDAC5; histone deacetylase 5 [KO:K11406] [EC:3.5.1.98]
101915175  MEF2A; myocyte enhancer factor 2A [KO:K09260]
101918367  MEF2B; myocyte enhancer factor 2B [KO:K09261]
101912452  MEF2C; myocyte enhancer factor 2C [KO:K04454]
101916931  MEF2D; myocyte enhancer factor 2D [KO:K09262]
101922518  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
101918546  SMAD2; SMAD family member 2 [KO:K04500]
101924726  SMAD3; SMAD family member 3 [KO:K23605]
101918184  SMAD4; SMAD family member 4 [KO:K04501]
101924446  mothers against decapentaplegic homolog 4-like [KO:K04501]
101915277  ACTA2; actin, alpha 2, smooth muscle, aorta [KO:K12313]
101922395  CTGF; connective tissue growth factor [KO:K06827]
101914229  connective tissue growth factor-like [KO:K06827]
101914397  AGTR1; angiotensin II receptor type 1 [KO:K04166]
106112248  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
  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
fpg04010  MAPK signaling pathway
fpg04020  Calcium signaling pathway
fpg04140  Autophagy - animal
fpg04150  mTOR signaling pathway
fpg04270  Vascular smooth muscle contraction
fpg04530  Tight junction
KO pathway
ko04371   
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