KEGG   PATHWAY: mdo04371
Entry
mdo04371                    Pathway                                
Name
Apelin signaling pathway - Monodelphis domestica (gray short-tailed opossum)
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
mdo04371  Apelin signaling pathway
mdo04371

Other DBs
GO: 0060183
Organism
Monodelphis domestica (gray short-tailed opossum) [GN:mdo]
Gene
100030463  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
100013164  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
100025332  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
100030872  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
100019274  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
100013823  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
100026554  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
100013831  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
100018346  ADCY10; adenylate cyclase 10, soluble [KO:K11265] [EC:4.6.1.1]
100011211  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
100026861  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100032298  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103104890  LIPE; lipase E, hormone sensitive type [KO:K07188] [EC:3.1.1.79]
103106486  APLN; apelin [KO:K05225]
103096091  APELA; apelin receptor early endogenous ligand [KO:K25355]
100025164  APLNR; apelin receptor [KO:K04174]
100031183  apelin receptor-like [KO:K04174]
100013052  GNAI1; G protein subunit alpha i1 [KO:K04630]
100030095  GNAI3; G protein subunit alpha i3 [KO:K04630]
100032986  GNAI2; G protein subunit alpha i2 [KO:K04630]
100010736  GNB1; G protein subunit beta 1 [KO:K04536]
100017392  GNB2; G protein subunit beta 2 [KO:K04537]
100013759  GNB3; G protein subunit beta 3 [KO:K07825]
100013546  GNB4; G protein subunit beta 4 [KO:K04538]
100031383  GNB5; G protein subunit beta 5 [KO:K04539]
100010452  GNG3; G protein subunit gamma 3 [KO:K04540]
100021132  GNG4; G protein subunit gamma 4 [KO:K04541]
100011015  GNG5; G protein subunit gamma 5 [KO:K04542]
100014687  GNG7; G protein subunit gamma 7 [KO:K04543]
100016961  GNG8; G protein subunit gamma 8 [KO:K04544]
100018189  GNG10; G protein subunit gamma 10 [KO:K04545]
100016914  GNG12; G protein subunit gamma 12 [KO:K04347]
100010184  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7-like [KO:K04347]
100017439  GNG13; G protein subunit gamma 13 [KO:K04547]
100018838  GNGT2; G protein subunit gamma transducin 2 [KO:K04549]
100011605  GNAQ; G protein subunit alpha q [KO:K04634]
100033281  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
100031660  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
100031869  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
100031263  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
100013305  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
100010212  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100025596  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100013232  RYR1; ryanodine receptor 1 [KO:K04961]
100028207  RYR2; ryanodine receptor 2 [KO:K04962]
100031570  RYR3; ryanodine receptor 3 [KO:K04963]
100021688  CALM3; calmodulin 3 [KO:K02183]
100018191  CALM1; calmodulin 1 [KO:K02183]
100032171  CALM2; calmodulin 2 [KO:K02183]
100025795  CALML4; calmodulin like 4 [KO:K02183]
100015722  calmodulin-alpha-like [KO:K02183]
100022649  calmodulin-alpha-like [KO:K02183]
100013712  NOS1; nitric oxide synthase 1 [KO:K13240] [EC:1.14.13.39]
100024271  NOS2; nitric oxide synthase 2 [KO:K13241] [EC:1.14.13.39]
100018035  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
100032210  PRKCE; protein kinase C epsilon [KO:K18050] [EC:2.7.11.13]
100017140  SLC9A1; solute carrier family 9 member A1 [KO:K05742]
100020329  SLC8A2; solute carrier family 8 member A2 [KO:K05849]
100010180  SLC8A1; solute carrier family 8 member A1 [KO:K05849]
100020311  SLC8A3; solute carrier family 8 member A3 [KO:K05849]
100015876  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
100021377  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
100019648  MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
100019715  MYL2; myosin light chain 2 [KO:K10351]
100018980  MYL3; myosin light chain 3 [KO:K12749]
100021133  MYL4; myosin light chain 4 [KO:K12750]
100032921  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
554186  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
554197  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
100022523  GTPase NRas-like [KO:K07828]
100030293  RRAS; related RAS viral (r-ras) oncogene homolog [KO:K07829]
100020614  RRAS2; related RAS viral (r-ras) oncogene homolog 2 [KO:K07830]
100017121  MRAS; muscle RAS oncogene homolog [KO:K07831]
100015410  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
100018410  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100018044  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100028096  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100012916  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100014573  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
100010269  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
100011566  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:2.7.11.1]
100010172  RPS6; ribosomal protein S6 [KO:K02991]
100009879  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
100012464  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
100014564  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
100019947  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
100027373  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
100619675  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
100618969  EGR1; early growth response 1 [KO:K09203]
100016723  SPP1; secreted phosphoprotein 1 [KO:K06250]
100033275  JAG1; jagged 1 [KO:K06052]
100012590  NOTCH3; notch 3 [KO:K20995]
100013257  CCND1; cyclin D1 [KO:K04503]
100029160  PDE3B; phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
100011397  PIK3C3; phosphatidylinositol 3-kinase catalytic subunit type 3 [KO:K00914] [EC:2.7.1.137]
100023836  PIK3R4; phosphoinositide-3-kinase regulatory subunit 4 [KO:K08333] [EC:2.7.11.1]
100010612  BECN1; beclin 1 [KO:K08334]
100018370  MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435]
100027672  MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435]
100028493  MAP1LC3A; microtubule associated protein 1 light chain 3 alpha [KO:K10435]
100019066  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.31]
100013711  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.31]
100014200  PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
100013848  PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
100018968  PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
100011008  PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
100032744  PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
100012952  PLIN1; perilipin 1 [KO:K08768]
100011263  PPARGC1A; PPARG coactivator 1 alpha [KO:K07202]
100015411  NRF1; nuclear respiratory factor 1 [KO:K11831]
103098724  TFAM; transcription factor A, mitochondrial [KO:K11830]
100014710  KLF2; Kruppel like factor 2 [KO:K17845]
100026664  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
100024566  GNA13; G protein subunit alpha 13 [KO:K04639]
100015956  CAMK4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
100019600  HDAC5; histone deacetylase 5 [KO:K11406] [EC:3.5.1.98]
100020349  MEF2A; myocyte enhancer factor 2A [KO:K09260]
100017177  MEF2B; myocyte enhancer factor 2B [KO:K09261]
100013140  MEF2C; myocyte enhancer factor 2C [KO:K04454]
100023326  MEF2D; myocyte enhancer factor 2D [KO:K09262]
100011507  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
100014493  SMAD2; SMAD family member 2 [KO:K04500]
100018703  SMAD3; SMAD family member 3 [KO:K23605]
100010143  SMAD4; SMAD family member 4 [KO:K04501]
100012397  ACTA2; actin, alpha 2, smooth muscle, aorta [KO:K12313]
100017854  actin-like [KO:K12313]
100027800  CDH1; cadherin 1 [KO:K05689]
100031049  CTGF; connective tissue growth factor [KO:K06827]
100017858  AGTR1; angiotensin II receptor type 1 [KO:K04166]
100017921  SERPINE1; serpin family E member 1 [KO:K03982]
100033029  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
mdo04010  MAPK signaling pathway
mdo04020  Calcium signaling pathway
mdo04140  Autophagy - animal
mdo04150  mTOR signaling pathway
mdo04151  PI3K-Akt signaling pathway
mdo04152  AMPK signaling pathway
mdo04270  Vascular smooth muscle contraction
mdo04530  Tight junction
mdo04923  Regulation of lipolysis in adipocytes
KO pathway
ko04371   
LinkDB

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