Entry Name Apelin signaling pathway
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 transductionBRITE hierarchy
Pathway map Other DBs Orthology K02991 RP-S6e, RPS6; small subunit ribosomal protein S6e
K03982 SERPINE1, PAI1; plasminogen activator inhibitor 1
K04166 AGTR1; angiotensin II receptor type 1
K04347 GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04454 MEF2C; MADS-box transcription enhancer factor 2C
K04500 SMAD2; mothers against decapentaplegic homolog 2
K04501 SMAD4; mothers against decapentaplegic homolog 4
K04503 CCND1; G1/S-specific cyclin-D1
K04536 GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537 GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K04538 GNB4; guanine nucleotide-binding protein subunit beta-4
K04539 GNB5; guanine nucleotide-binding protein subunit beta-5
K04540 GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541 GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542 GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543 GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544 GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545 GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546 GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04547 GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548 GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549 GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K04630 GNAI; guanine nucleotide-binding protein G(i) subunit alpha
K04634 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04639 GNA13; guanine nucleotide-binding protein subunit alpha-13
K04958 ITPR1; inositol 1,4,5-triphosphate receptor type 1
K04959 ITPR2; inositol 1,4,5-triphosphate receptor type 2
K04960 ITPR3; inositol 1,4,5-triphosphate receptor type 3
K04961 RYR1; ryanodine receptor 1
K04962 RYR2; ryanodine receptor 2
K04963 RYR3; ryanodine receptor 3
K05689 CDH1, CDHE, CD324; cadherin 1, type 1, E-cadherin
K05742 SLC9A1, NHE1; solute carrier family 9 (sodium/hydrogen exchanger), member 1
K05849 SLC8A, NCX; solute carrier family 8 (sodium/calcium exchanger)
K05869 CAMK4; calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17 ]
K06250 SPP1, BNSP, OPN; secreted phosphoprotein 1
K06827 CTGF, CCN2, IGFBP8; connective tissue growth factor (insulin-like growth factor-binding protein 8)
K07198 PRKAA, AMPK; 5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31 ]
K07199 PRKAB; 5'-AMP-activated protein kinase, regulatory beta subunit
K07200 PRKAG; 5'-AMP-activated protein kinase, regulatory gamma subunit
K07202 PPARGC1A, PGC1A; alpha peroxisome proliferator-activated receptor gamma coactivator 1-alpha
K07203 MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1 ]
K07825 GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K07826 GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K07827 KRAS, KRAS2; GTPase KRas
K07829 RRAS; Ras-related protein R-Ras
K07830 RRAS2, TC21; Ras-related protein R-Ras2
K07831 MRAS; Ras-related protein M-Ras
K08333 PIK3R4, VPS15; phosphoinositide-3-kinase, regulatory subunit 4 [EC:2.7.11.1 ]
K08334 BECN, VPS30, ATG6; beclin
K08769 UCP1, SLC25A7; solute carrier family 25 (mitochondrial uncoupling protein), member 7
K09203 EGR1; early growth response protein 1
K09260 MEF2A; MADS-box transcription enhancer factor 2A
K09261 MEF2B; MADS-box transcription enhancer factor 2B
K09262 MEF2D; MADS-box transcription enhancer factor 2D
K10351 MYL2; myosin regulatory light chain 2
K10435 MAP1LC; microtubule-associated protein 1 light chain
K11830 TFAM, MTTFA; transcription factor A, mitochondrial
K11831 NRF1; nuclear respiratory factor 1
K12313 ACTA2; actin, aortic smooth muscle
K12749 MYL3; myosin light chain 3
K12750 MYL4; myosin light chain 4
K13296 PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [EC:3.1.4.17 ]
K17845 KLF2; krueppel-like factor 2
K21289 PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [EC:2.7.1.153 ]
K21290 PIK3R5_6; phosphoinositide-3-kinase regulatory subunit 5/6
K23605 SMAD3; mothers against decapentaplegic homolog 3
K25355 APELA; apelin receptor early endogenous ligand
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
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 Reference Authors Andersen CU, Hilberg O, Mellemkjaer S, Nielsen-Kudsk JE, Simonsen U
Title Apelin and pulmonary hypertension.
Journal 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 Reference Authors Japp AG, Newby DE
Title The apelin-APJ system in heart failure: pathophysiologic relevance and therapeutic potential.
Journal Reference Authors Folino A, Montarolo PG, Samaja M, Rastaldo R
Title Effects of apelin on the cardiovascular system.
Journal 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 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 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 Reference Authors Castan-Laurell I, Dray C, Attane C, Duparc T, Knauf C, Valet P
Title Apelin, diabetes, and obesity.
Journal 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 Reference Authors Wu D, He L, Chen L
Title Apelin/APJ system: a promising therapy target for hypertension.
Journal 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 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 Reference Authors Lu L, Wu D, Li L, Chen L
Title Apelin/APJ system: A bifunctional target for cardiac hypertrophy.
Journal Reference Authors Carmen GY, Victor SM
Title Signalling mechanisms regulating lipolysis.
Journal Reference Authors Hu H, He L, Li L, Chen L
Title Apelin/APJ system as a therapeutic target in diabetes and its complications.
Journal Reference Authors Bertrand C, Valet P, Castan-Laurell I
Title Apelin and energy metabolism.
Journal 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 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 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 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 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 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 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 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 Reference Authors Huang S, Chen L, Lu L, Li L
Title The apelin-APJ axis: A novel potential therapeutic target for organ fibrosis.
Journal 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 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 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 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 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 Related ko04270 Vascular smooth muscle contraction
ko04923 Regulation of lipolysis in adipocytes
