KEGG   PATHWAY: lcm04371
Entry
lcm04371                    Pathway                                
Name
Apelin signaling pathway - Latimeria chalumnae (coelacanth)
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
lcm04371  Apelin signaling pathway
lcm04371

Other DBs
GO: 0060183
Organism
Latimeria chalumnae (coelacanth) [GN:lcm]
Gene
102367170  adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
102365947  adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
102353581  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102366154  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102351065  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102346737  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102363182  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102366360  ADCY10; adenylate cyclase 10, soluble [KO:K11265] [EC:4.6.1.1]
102359855  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
102362951  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102346636  LIPE; lipase E, hormone sensitive type [KO:K07188] [EC:3.1.1.79]
106702803  APLN; apelin [KO:K05225]
102356079  APELA; apelin receptor early endogenous ligand [KO:K25355]
102354490  apelin receptor A-like [KO:K04174]
102356591  APLNR; apelin receptor [KO:K04174]
102362833  GNAI3; G protein subunit alpha i3 [KO:K04630]
102361424  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
102364585  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
102367354  GNB1; G protein subunit beta 1 [KO:K04536]
102348681  GNB3; G protein subunit beta 3 [KO:K07825]
102350687  GNB4; G protein subunit beta 4 [KO:K04538]
102360347  GNB5; G protein subunit beta 5 [KO:K04539]
102347084  GNG2; G protein subunit gamma 2 [KO:K07826]
102353070  GNG3; G protein subunit gamma 3 [KO:K04540]
102361158  GNG5; G protein subunit gamma 5 [KO:K04542]
102359885  GNG7; G protein subunit gamma 7 [KO:K04543]
102359168  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7-like [KO:K04543]
102345532  GNG8; G protein subunit gamma 8 [KO:K04544]
102359579  GNG10; G protein subunit gamma 10 [KO:K04545]
102365300  guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04546]
102348748  GNG12; G protein subunit gamma 12 [KO:K04347]
102366512  GNG13; G protein subunit gamma 13 [KO:K04547]
102345332  GNGT2; G protein subunit gamma transducin 2 [KO:K04549]
102359416  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102352409  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04634]
102365542  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102345855  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102348275  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102362364  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102361301  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102359880  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102349825  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102356360  RYR1; ryanodine receptor 1 [KO:K04961]
102353265  RYR2; ryanodine receptor 2 [KO:K04962]
102364131  RYR3; ryanodine receptor 3 [KO:K04963]
102345989  parvalbumin beta-like [KO:K02183]
102366907  CALML6; calmodulin like 6 [KO:K02183]
102360791  calmodulin [KO:K02183]
102347246  CALM1; calmodulin 1 [KO:K02183]
102359711  CALM2; calmodulin 2 [KO:K02183]
102361286  calmodulin [KO:K02183]
102359693  CALML4; calmodulin like 4 [KO:K02183]
102348281  NOS1; nitric oxide synthase 1 [KO:K13240] [EC:1.14.13.39]
102354990  NOS2; nitric oxide synthase 2 [KO:K13241] [EC:1.14.13.39]
102363817  protein kinase C epsilon type-like [KO:K18050] [EC:2.7.11.13]
102351735  SLC9A1; solute carrier family 9 member A1 [KO:K05742]
102353683  SLC8A2; solute carrier family 8 member A2 [KO:K05849]
102367281  sodium/calcium exchanger 1-like [KO:K05849]
102347694  SLC8A3; solute carrier family 8 member A3 [KO:K05849]
102358533  SLC8A1; solute carrier family 8 member A1 [KO:K05849]
102346967  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
102352251  myosin light chain kinase 3-like [KO:K00907] [EC:2.7.11.18]
102362592  MYL2; myosin light chain 2 [KO:K10351]
102358075  MYL3; myosin light chain 3 [KO:K12749]
102358220  MYL4; myosin light chain 4 [KO:K12750]
102355427  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102352473  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102357700  GTPase HRas-like [KO:K07827]
102361045  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102358831  RRAS2; related RAS viral (r-ras) oncogene homolog 2 [KO:K07830]
102349532  RRAS; related RAS viral (r-ras) oncogene homolog [KO:K07830]
102359118  MRAS; muscle RAS oncogene homolog [KO:K07831]
102356108  ras-related protein M-Ras-like [KO:K07831]
102357545  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102358560  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102350370  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102355992  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102354262  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102353676  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
102361574  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:2.7.11.1]
102347556  RPS6; ribosomal protein S6 [KO:K02991]
102362971  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform-like [KO:K21289] [EC:2.7.1.153]
102353565  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
102361229  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
102361486  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
102359797  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102359272  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102346546  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102360124  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
102366110  EGR1; early growth response 1 [KO:K09203]
102353922  SPP1; osteopontin [KO:K06250]
102364713  JAG1; jagged 1 [KO:K06052]
102353790  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
102366854  neurogenic locus notch homolog protein 2 [KO:K20995]
102361167  CCND1; cyclin D1 [KO:K04503]
102367471  G1/S-specific cyclin-D1-like [KO:K04503]
102357842  PDE3B; phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
102353717  PIK3C3; phosphatidylinositol 3-kinase catalytic subunit type 3 [KO:K00914] [EC:2.7.1.137]
102349203  PIK3R4; phosphoinositide-3-kinase regulatory subunit 4 [KO:K08333] [EC:2.7.11.1]
102346746  BECN1; beclin 1 [KO:K08334]
102365528  MAP1LC3A; microtubule associated protein 1 light chain 3 alpha [KO:K10435]
102363169  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
102358729  MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435]
102345225  MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435]
102365637  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.31]
102349521  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.31]
102350587  PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
102345693  PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
102348610  PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
102345950  PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
102366003  PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
102365544  PLIN1; perilipin 1 [KO:K08768]
102366009  PPARGC1A; PPARG coactivator 1 alpha [KO:K07202]
102349378  NRF1; nuclear respiratory factor 1 [KO:K11831]
102350734  TFAM; transcription factor A, mitochondrial [KO:K11830]
102355178  KLF2; Kruppel like factor 2 [KO:K17845]
102350955  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
102367258  SPHK2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
102364864  GNA13; G protein subunit alpha 13 [KO:K04639]
102362167  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
102361440  calcium/calmodulin-dependent protein kinase type IV-like [KO:K05869] [EC:2.7.11.17]
102360989  HDAC5; histone deacetylase 5 [KO:K11406] [EC:3.5.1.98]
102357880  HDAC4; histone deacetylase 4 [KO:K11406] [EC:3.5.1.98]
102348604  MEF2A; myocyte enhancer factor 2A [KO:K09260]
102361694  MEF2C; myocyte enhancer factor 2C [KO:K04454]
102346045  MEF2D; myocyte enhancer factor 2D [KO:K09262]
102350402  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
102360430  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
102356317  SMAD3; SMAD family member 3 [KO:K23605]
102358988  mothers against decapentaplegic homolog 4-like [KO:K04501]
102353847  SMAD4; SMAD family member 4 [KO:K04501]
102352432  actin, aortic smooth muscle-like [KO:K12313]
102349699  ACTA2; actin, alpha 2, smooth muscle, aorta [KO:K12313]
102364978  B-cadherin-like [KO:K05689]
102359919  cadherin-1-like [KO:K05689]
102361385  CDH1; cadherin 1 [KO:K05689]
102365602  connective tissue growth factor-like [KO:K06827]
102363650  CTGF; connective tissue growth factor [KO:K06827]
102347667  AGTR1; angiotensin II receptor type 1 [KO:K04166]
102360184  SERPINE1; serpin family E member 1 [KO:K03982]
102346134  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
lcm04010  MAPK signaling pathway
lcm04020  Calcium signaling pathway
lcm04140  Autophagy - animal
lcm04150  mTOR signaling pathway
lcm04270  Vascular smooth muscle contraction
lcm04530  Tight junction
KO pathway
ko04371   
LinkDB

DBGET integrated database retrieval system