KEGG   PATHWAY: cvf04371
Entry
cvf04371                    Pathway                                
Name
Apelin signaling pathway - Charadrius vociferus (killdeer)
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
cvf04371  Apelin signaling pathway
cvf04371

Other DBs
GO: 0060183
Organism
Charadrius vociferus (killdeer) [GN:cvf]
Gene
104295315  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
104285350  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
104295685  ADCY3; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
104288498  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
104284823  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
104286482  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
104282884  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
104283743  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
104286144  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
104292946  guanine nucleotide-binding protein G(k) subunit alpha-like [KO:K04630]
104284574  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
104288878  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
104290505  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
104292999  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 isoform X1 [KO:K07825]
104295545  GNB4; guanine nucleotide-binding protein subunit beta-4 isoform X1 [KO:K04538]
104287100  GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
104294304  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
104287253  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
104286302  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
104283893  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
104295601  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
104285500  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
104289582  GNG13; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
104292779  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
104289948  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
104284360  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
104292993  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
104287337  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
104287385  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
104284516  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
104281650  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
104289376  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
104294087  RYR2; ryanodine receptor 2 [KO:K04962]
104288222  RYR3; ryanodine receptor 3 [KO:K04963]
104292668  CALML4; calmodulin-like protein 4 [KO:K02183]
104290389  calmodulin-like [KO:K02183]
104282562  CALM2; calmodulin [KO:K02183]
104284618  CALML5; calmodulin-like protein 5 [KO:K02183]
104286947  CALM1; LOW QUALITY PROTEIN: calmodulin [KO:K02183]
104288003  NOS1; nitric oxide synthase, brain [KO:K13240] [EC:1.14.13.39]
104283292  NOS2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
104282541  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
104283960  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
104293047  SLC8A1; sodium/calcium exchanger 1 isoform X1 [KO:K05849]
104283872  SLC8A3; sodium/calcium exchanger 3 isoform X1 [KO:K05849]
104281937  LOW QUALITY PROTEIN: sodium/calcium exchanger 2-like [KO:K05849]
104288459  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
104286656  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
104293989  MYLK2; LOW QUALITY PROTEIN: myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
104294452  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
104285296  myosin light chain kinase, smooth muscle-like [KO:K00907] [EC:2.7.11.18]
104282221  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
104282417  MYL3; myosin light chain 3 [KO:K12749]
104285387  MYL4; myosin light chain 4 [KO:K12750]
104290283  HRAS; GTPase HRas [KO:K02833]
104281647  KRAS; GTPase KRas isoform X1 [KO:K07827]
104289524  NRAS; GTPase NRas [KO:K07828]
104291693  RRAS2; ras-related protein R-Ras2 [KO:K07830]
104288472  MRAS; ras-related protein M-Ras [KO:K07831]
104290771  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
104288536  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
104282773  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
104289233  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104284358  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
104292183  RPS6; 40S ribosomal protein S6 [KO:K02991]
104291598  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
104281940  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
104281941  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
104283204  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104285124  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104294083  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104290455  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
104282783  EGR1; LOW QUALITY PROTEIN: early growth response protein 1 [KO:K09203]
104291509  SPP1; osteopontin [KO:K06250]
104287344  JAG1; protein jagged-1 [KO:K06052]
104287532  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
104291710  PDE3B; LOW QUALITY PROTEIN: cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
104292260  PIK3C3; phosphatidylinositol 3-kinase catalytic subunit type 3 [KO:K00914] [EC:2.7.1.137]
104281571  PIK3R4; phosphoinositide 3-kinase regulatory subunit 4 [KO:K08333] [EC:2.7.11.1]
104292209  BECN1; beclin-1 [KO:K08334]
104292705  MAP1LC3A; LOW QUALITY PROTEIN: microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
104290862  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
104294079  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
104296013  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
104286230  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
104295005  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
104289631  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199]
104293318  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
104285336  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
104288033  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
104284815  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
104287397  PLIN1; perilipin-1 [KO:K08768]
104288776  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha [KO:K07202]
104284628  NRF1; nuclear respiratory factor 1 isoform X1 [KO:K11831]
104295444  KLF2; Krueppel-like factor 2 [KO:K17845]
104295068  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
104286012  calcium/calmodulin-dependent protein kinase type IV-like [KO:K05869] [EC:2.7.11.17]
104294250  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
104290017  HDAC4; LOW QUALITY PROTEIN: histone deacetylase 4 [KO:K11406] [EC:3.5.1.98]
104288260  MEF2A; myocyte-specific enhancer factor 2A isoform X1 [KO:K09260]
104288101  MEF2C; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454]
104284109  LOW QUALITY PROTEIN: myocyte-specific enhancer factor 2C-like [KO:K04454]
104292657  MEF2D; LOW QUALITY PROTEIN: myocyte-specific enhancer factor 2D [KO:K09262]
104295278  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
104291926  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
104288041  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
104285280  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
104289714  ACTA2; actin, aortic smooth muscle isoform X1 [KO:K12313]
104289403  connective tissue growth factor-like [KO:K06827]
104282095  CTGF; connective tissue growth factor [KO:K06827]
104284992  AGTR1; type-1 angiotensin II receptor [KO:K04166]
104285150  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
cvf04010  MAPK signaling pathway
cvf04020  Calcium signaling pathway
cvf04140  Autophagy - animal
cvf04150  mTOR signaling pathway
cvf04270  Vascular smooth muscle contraction
cvf04530  Tight junction
KO pathway
ko04371   
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