Endothelin pathway (Homo sapiens)

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KSR1S39245GRB218SOS56EGFRY1173PY845Y1068CYIGFBP5ACTA2MPP5ISCA1GJC1HOPXTNFRAC1RGS3EPHA2BCAR3DLATPTGS2DAZAP2MMP1P4HBSDC1GNAQCXCL8DNAJC12ITGB3COL5A1CALD1CDH1MAP3K2IRX4CTNNB1PPP1R12APLOD2COL7A1ARL6IP5FNDC1 MPPED2HIF1ABMI1ZNF136FGF2RDXBCAR1THBS1HLA-AGSNTIMP3 CCND1MMP9GAB1WNK1WIPF1MED12NPPBBCL2ITGA5PLCB1FASTKD1CDH2IL11ITGA2ADAM12ADAM19COMPCRYZL1MYL12BCDH1ZNF131YWHAQFOXK2ITGB1BP1MARCKSMYO1BDNAJC10ATRXTPM1PXNVIL1ACTR1ATRIOBPARRB1COL9A1FHL2COL1A4GOLGB1FNDC3BACTG2E2F3GJA5ITGB3COL1A2B3GNT2CREG1EIF5BRUNX1TWIST1EMC1FLNBMMP2ITGB1VIMANXA7RAB5CKDM5BSP4ZFYVE16PTK2BTRAFD1ARHGEF7ITGB3ACTR3MINK1CCL2GULP1GALNT1NOX5MYBPC3ARPC4ITGA2NPPATPM4COL4A1FLNCSTOMIGFBP4ACTR2NKX2-5ACTA2EZRIPK1SMAD5TNS1CCN2NQO1ARRB1HTATSF1GSTA5CAPZBCOL1A3NAA16GGA2SNAI1WWTR1VCANABHD3MMP3SSH1NOL8CCNB1COL1A1IL1BATP6V1HCTNNB1KLHL20NAA50TAGLN21251111435T1812491221545S199, 516428Y1651Y24932G-protein dependentEDN1EDN1EDN1EDNRA15EDNRBROCK165RAC129PAK1P29MAPK866, 68RHOCT18344DAG1PLCB113PKC29Ca2+SRCT41620T418KRAS23RAF156MAP2K1S21770MAP2K2S22162MAPK1T20211MAPK3Y20411NFKBIA79S36S32RELA79S536NFKB1ARHGAP35S115038HIF1A28PIK3CA74PILK30AKT1T3087, 31, 69S473b-arrestin dependentLIMKT508T50544MTORS2448 34PRKACA43CREBP3, 53PPP3CA41NFATC137CREB1S13353MAPK14P9, 47RELA52NFKB1NUCYNURPS6KB1P73HSPB157S85GATA458MEF2A55CALM15CASP851Blood vesselcontractionRPS6S236S23534ATF24CDC4229SHCP18IRS1PNOS316, 59S1179S1177PRKCA23IP3ARF677ELK110PATF110S63RPS6KA2S38110RPS6KA3T577 10MAPK9Y18517, 60, 66JUNS63S7378CYNUEP2EP4CFL122, 44S3ActinpolymerizationCytoskeletalpolymerisationPulmonary hypertensionMMP2MMP9CellinvasionCell invasionVCAM1CX3CL1Renal fibrosisPTGS2CXCL1CXCL8Metastasisand tumorprogressionMCAMInvasionand metastasisMYH11Smooth muscledifferentiationCell migrationIL6GATA4MMP13FOSJUNEGR1CSF2CDH1CTNND1CTNNB1CCND1COX1COX2PLA22Cell survivaland angiogenesisEDN3YAP1P75Epithelial to mesenchymaltransition (EMT)SRCSRC32Y418Y416ARRB132, 44SRCT416T418ARRB1EDNRAARHGEF11HypoxiaELK110, 50AXIN132GSK3BP32TCF432PADAM17ADIPOQ76MLCK49PPP1R14A64T38PPP1R12AGNAST853T6956446JAK1P8STAT38, 53Y705CHUKIKBKB34S18034S187KCNK3MMP1467MSNECM contractionRAP1GAPRHOA1239ABL16Y412SREEP30072CREB153S133ATF1S6310ATF2S734BADS112CALD1S79063S759CAMK2AT28672CAMK2G24T305HDAC542HDAC5P42CDKN1B27S10CDK2CFL22761PPTK2Y397AXIN1EIF2BP40FLI16T312FOS25S33FOXO348T32FYN19Y416MLC36, 71T18S19BCL2Lung fibrosisCellular proliferation, migration and contraction in colon cancer adjacent fibroblastsCCS differentiationEP300VEGFANOS3NO accumulationCX3CL1CTNND1 Cardiac hypertrophy51LEPRChemo protectionBrain inflamation disordersInflammationCYNUCYNUCCL2CXCL1GLSSHC1CTNNB1S3648ARHGEF726ARHGEF729COL1A229CytoplasmNucleusGNA13GNA12GNAQGNA13GNA12LEGENDLigandReceptorLeads to unknown mechanismPositive regulation of gene expressionNegative regulation of gene expressionTranslocationInhibitionPlasma membraneCytoplasmNucleusPMCPNUInduced CatalysisActivationProteinProtein-Protein InteractionProteinmRNAEnzyme complex


Description

Endothelin is a strong peptide well known for its vasoconstriction activities. It is known for regulating extensive physiological and pathophysiological activities with beneficial and detrimental roles in mammals.To develop this network map of endothelin mediated signalling pathway, We searched term retrieved 2,800 papers in Pubmed were used for initial screening. Of these, 640 research articles were screened for endothelin mediated reactions and selected for annotation. Out of these, 334 articles had information which are compatible to endothelin mediated signalling were selected for further curation. The manual curation of selected articles documented 90 activation / inhibition events, 98 PTM or catalysis events, 56molecular associations, 239 gene regulation events, 145 types of protein expression and 27 protein translocation events.

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  1. Tokudome T, Horio T, Soeki T, Mori K, Kishimoto I, Suga S, Yoshihara F, Kawano Y, Kohno M, Kangawa K; ''Inhibitory effect of C-type natriuretic peptide (CNP) on cultured cardiac myocyte hypertrophy: interference between CNP and endothelin-1 signaling pathways.''; Endocrinology, 2004 PubMed Europe PMC Scholia
  2. Goto A, Sumiyama K, Kamioka Y, Nakasyo E, Ito K, Iwasaki M, Enomoto H, Matsuda M; ''GDNF and endothelin 3 regulate migration of enteric neural crest-derived cells via protein kinase A and Rac1.''; J Neurosci, 2013 PubMed Europe PMC Scholia
  3. Di Nunzio AS, Jaureguiberry MS, Rodano V, Bianciotti LG, Vatta MS; ''Endothelin-1 and -3 diminish neuronal NE release through an NO mechanism in rat anterior hypothalamus.''; Am J Physiol Regul Integr Comp Physiol, 2002 PubMed Europe PMC Scholia
  4. Chahdi A, Sorokin A; ''The role of beta(1)Pix/caveolin-1 interaction in endothelin signaling through Galpha subunits.''; Biochem Biophys Res Commun, 2010 PubMed Europe PMC Scholia
  5. Hinsley EE, Hunt S, Hunter KD, Whawell SA, Lambert DW; ''Endothelin-1 stimulates motility of head and neck squamous carcinoma cells by promoting stromal-epithelial interactions.''; Int J Cancer, 2012 PubMed Europe PMC Scholia
  6. Yamboliev IA, Gerthoffer WT; ''Modulatory role of ERK MAPK-caldesmon pathway in PDGF-stimulated migration of cultured pulmonary artery SMCs.''; Am J Physiol Cell Physiol, 2001 PubMed Europe PMC Scholia
  7. Wu MH, Huang CY, Lin JA, Wang SW, Peng CY, Cheng HC, Tang CH; ''Endothelin-1 promotes vascular endothelial growth factor-dependent angiogenesis in human chondrosarcoma cells.''; Oncogene, 2014 PubMed Europe PMC Scholia
  8. Tang B, Li Y, Nagaraj C, Morty RE, Gabor S, Stacher E, Voswinckel R, Weissmann N, Leithner K, Olschewski H, Olschewski A; ''Endothelin-1 inhibits background two-pore domain channel TASK-1 in primary human pulmonary artery smooth muscle cells.''; Am J Respir Cell Mol Biol, 2009 PubMed Europe PMC Scholia
  9. Glenn DJ, Rahmutula D, Nishimoto M, Liang F, Gardner DG; ''Atrial natriuretic peptide suppresses endothelin gene expression and proliferation in cardiac fibroblasts through a GATA4-dependent mechanism.''; Cardiovasc Res, 2009 PubMed Europe PMC Scholia
  10. Hunter JC, Zeidan A, Javadov S, Kilic A, Rajapurohitam V, Karmazyn M; ''Nitric oxide inhibits endothelin-1-induced neonatal cardiomyocyte hypertrophy via a RhoA-ROCK-dependent pathway.''; J Mol Cell Cardiol, 2009 PubMed Europe PMC Scholia
  11. Chahdi A, Sorokin A; ''Endothelin-1 couples betaPix to p66Shc: role of betaPix in cell proliferation through FOXO3a phosphorylation and p27kip1 down-regulation independently of Akt.''; Mol Biol Cell, 2008 PubMed Europe PMC Scholia
  12. Kakita T, Hasegawa K, Iwai-Kanai E, Adachi S, Morimoto T, Wada H, Kawamura T, Yanazume T, Sasayama S; ''Calcineurin pathway is required for endothelin-1-mediated protection against oxidant stress-induced apoptosis in cardiac myocytes.''; Circ Res, 2001 PubMed Europe PMC Scholia
  13. Tocci P, Caprara V, Cianfrocca R, Sestito R, Di Castro V, Bagnato A, Rosano L; ''Endothelin-1/endothelin A receptor axis activates RhoA GTPase in epithelial ovarian cancer.''; Life Sci, 2016 PubMed Europe PMC Scholia
  14. Seccia TM, Caroccia B, Gioco F, Piazza M, Buccella V, Guidolin D, Guerzoni E, Montini B, Petrelli L, Pagnin E, Ravarotto V, Belloni AS, Calo LA, Rossi GP; ''Endothelin-1 Drives Epithelial-Mesenchymal Transition in Hypertensive Nephroangiosclerosis.''; J Am Heart Assoc, 2016 PubMed Europe PMC Scholia
  15. Cazaubon S, Chaverot N, Romero IA, Girault JA, Adamson P, Strosberg AD, Couraud PO; ''Growth factor activity of endothelin-1 in primary astrocytes mediated by adhesion-dependent and -independent pathways.''; J Neurosci, 1997 PubMed Europe PMC Scholia
  16. Jozsef L, Khreiss T, Fournier A, Chan JS, Filep JG; ''Extracellular signal-regulated kinase plays an essential role in endothelin-1-induced homotypic adhesion of human neutrophil granulocytes.''; Br J Pharmacol, 2002 PubMed Europe PMC Scholia
  17. Nakagawa Y, Kuwahara K, Harada M, Takahashi N, Yasuno S, Adachi Y, Kawakami R, Nakanishi M, Tanimoto K, Usami S, Kinoshita H, Saito Y, Nakao K; ''Class II HDACs mediate CaMK-dependent signaling to NRSF in ventricular myocytes.''; J Mol Cell Cardiol, 2006 PubMed Europe PMC Scholia
  18. Gerstung M, Roth T, Dienes HP, Licht C, Fries JW; ''Endothelin-1 induces NF-kappaB via two independent pathways in human renal tubular epithelial cells.''; Am J Nephrol, 2007 PubMed Europe PMC Scholia
  19. Son GY, Bak EJ, Kim JH, Lee DE, Kang SM, Lee SY, Choi L, Sun JS, Kim SK, Park W, Kim BI, Yoo YJ, Chang I, Shin DM; ''Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines.''; PLoS One, 2016 PubMed Europe PMC Scholia
  20. Javadov S, Rajapurohitam V, Kilic A, Zeidan A, Choi A, Karmazyn M; ''Anti-hypertrophic effect of NHE-1 inhibition involves GSK-3beta-dependent attenuation of mitochondrial dysfunction.''; J Mol Cell Cardiol, 2009 PubMed Europe PMC Scholia
  21. Shah BH, Baukal AJ, Chen HD, Shah AB, Catt KJ; ''Mechanisms of endothelin-1-induced MAP kinase activation in adrenal glomerulosa cells.''; J Steroid Biochem Mol Biol, 2006 PubMed Europe PMC Scholia
  22. Akamata K, Asano Y, Aozasa N, Noda S, Taniguchi T, Takahashi T, Ichimura Y, Toyama T, Sato S; ''Bosentan reverses the pro-fibrotic phenotype of systemic sclerosis dermal fibroblasts via increasing DNA binding ability of transcription factor Fli1.''; Arthritis Res Ther, 2014 PubMed Europe PMC Scholia
  23. Masamune A, Satoh M, Kikuta K, Suzuki N, Shimosegawa T; ''Endothelin-1 stimulates contraction and migration of rat pancreatic stellate cells.''; World J Gastroenterol, 2005 PubMed Europe PMC Scholia
  24. Karoor V, Fini MA, Loomis Z, Sullivan T, Hersh LB, Gerasimovskaya E, Irwin D, Dempsey EC; ''Sustained Activation of Rho GTPases Promotes a Synthetic Pulmonary Artery Smooth Muscle Cell Phenotype in Neprilysin Null Mice.''; Arterioscler Thromb Vasc Biol, 2018 PubMed Europe PMC Scholia
  25. Isono M, Haneda M, Maeda S, Omatsu-Kanbe M, Kikkawa R; ''Atrial natriuretic peptide inhibits endothelin-1-induced activation of JNK in glomerular mesangial cells.''; Kidney Int, 1998 PubMed Europe PMC Scholia
  26. Tong XK, Hamel E; ''Transforming growth factor-beta 1 impairs endothelin-1-mediated contraction of brain vessels by inducing mitogen-activated protein (MAP) kinase phosphatase-1 and inhibiting p38 MAP kinase.''; Mol Pharmacol, 2007 PubMed Europe PMC Scholia
  27. Bao Y, Li R, Jiang J, Cai B, Gao J, Le K, Zhang F, Chen S, Liu P; ''Activation of peroxisome proliferator-activated receptor gamma inhibits endothelin-1-induced cardiachypertrophy via the calcineurin/NFAT signaling pathway.''; Mol Cell Biochem, 2008 PubMed Europe PMC Scholia
  28. Wu MH, Chen LM, Hsu HH, Lin JA, Lin YM, Tsai FJ, Tsai CH, Huang CY, Tang CH; ''Endothelin-1 enhances cell migration through COX-2 up-regulation in human chondrosarcoma.''; Biochim Biophys Acta, 2013 PubMed Europe PMC Scholia
  29. Iizuka M, Murata T, Hori M, Ozaki H; ''Increased contractility of hepatic stellate cells in cirrhosis is mediated by enhanced Ca2+-dependent and Ca2+-sensitization pathways.''; Am J Physiol Gastrointest Liver Physiol, 2011 PubMed Europe PMC Scholia
  30. Li B, Kaetzel MA, Dedman JR; ''Signaling pathways regulating murine cardiac CREB phosphorylation.''; Biochem Biophys Res Commun, 2006 PubMed Europe PMC Scholia
  31. Jamal S, Schneider RJ; ''UV-induction of keratinocyte endothelin-1 downregulates E-cadherin in melanocytes and melanoma cells.''; J Clin Invest, 2002 PubMed Europe PMC Scholia
  32. Deng H, Hershenson MB, Lei J, Anyanwu AC, Pinsky DJ, Bentley JK; ''Pulmonary artery smooth muscle hypertrophy: roles of glycogen synthase kinase-3beta and p70 ribosomal S6 kinase.''; Am J Physiol Lung Cell Mol Physiol, 2010 PubMed Europe PMC Scholia
  33. Araki S, Haneda M, Togawa M, Kikkawa R; ''Endothelin-1 activates c-Jun NH2-terminal kinase in mesangial cells.''; Kidney Int, 1997 PubMed Europe PMC Scholia
  34. Takahashi H, Takeishi Y, Seidler T, Arimoto T, Akiyama H, Hozumi Y, Koyama Y, Shishido T, Tsunoda Y, Niizeki T, Nozaki N, Abe J, Hasenfuss G, Goto K, Kubota I; ''Adenovirus-mediated overexpression of diacylglycerol kinase-zeta inhibits endothelin-1-induced cardiomyocyte hypertrophy.''; Circulation, 2005 PubMed Europe PMC Scholia
  35. Rosano L, Spinella F, Di Castro V, Nicotra MR, Dedhar S, de Herreros AG, Natali PG, Bagnato A; ''Endothelin-1 promotes epithelial-to-mesenchymal transition in human ovarian cancer cells.''; Cancer Res, 2005 PubMed Europe PMC Scholia
  36. Tang YC, Liu CW, Chang HH, Juan CC, Kuo YC, Kao CC, Huang YM, Kao YH; ''Endothelin-1 stimulates resistin gene expression.''; Endocrinology, 2014 PubMed Europe PMC Scholia
  37. Wang L, Proud CG; ''Ras/Erk signaling is essential for activation of protein synthesis by Gq protein-coupled receptor agonists in adult cardiomyocytes.''; Circ Res, 2002 PubMed Europe PMC Scholia
  38. Montezano AC, Burger D, Paravicini TM, Chignalia AZ, Yusuf H, Almasri M, He Y, Callera GE, He G, Krause KH, Lambeth D, Quinn MT, Touyz RM; ''Nicotinamide adenine dinucleotide phosphate reduced oxidase 5 (Nox5) regulation by angiotensin II and endothelin-1 is mediated via calcium/calmodulin-dependent, rac-1-independent pathways in human endothelial cells.''; Circ Res, 2010 PubMed Europe PMC Scholia
  39. Gadea A, Schinelli S, Gallo V; ''Endothelin-1 regulates astrocyte proliferation and reactive gliosis via a JNK/c-Jun signaling pathway.''; J Neurosci, 2008 PubMed Europe PMC Scholia
  40. Weng CM, Yu CC, Kuo ML, Chen BC, Lin CH; ''Endothelin-1 induces connective tissue growth factor expression in human lung fibroblasts by ETAR-dependent JNK/AP-1 pathway.''; Biochem Pharmacol, 2014 PubMed Europe PMC Scholia
  41. Foschi M, Chari S, Dunn MJ, Sorokin A; ''Biphasic activation of p21ras by endothelin-1 sequentially activates the ERK cascade and phosphatidylinositol 3-kinase.''; EMBO J, 1997 PubMed Europe PMC Scholia
  42. Takagi Y, Ninomiya H, Sakamoto A, Miwa S, Masaki T; ''Structural basis of G protein specificity of human endothelin receptors. A study with endothelinA/B chimeras.''; J Biol Chem, 1995 PubMed Europe PMC Scholia
  43. Mori K, Amano M, Takefuji M, Kato K, Morita Y, Nishioka T, Matsuura Y, Murohara T, Kaibuchi K; ''Rho-kinase contributes to sustained RhoA activation through phosphorylation of p190A RhoGAP.''; J Biol Chem, 2009 PubMed Europe PMC Scholia
  44. McWhinnie R, Pechkovsky DV, Zhou D, Lane D, Halayko AJ, Knight DA, Bai TR; ''Endothelin-1 induces hypertrophy and inhibits apoptosis in human airway smooth muscle cells.''; Am J Physiol Lung Cell Mol Physiol, 2007 PubMed Europe PMC Scholia
  45. Cianfrocca R, Rosano L, Spinella F, Di Castro V, Natali PG, Bagnato A; ''Beta-arrestin-1 mediates the endothelin-1-induced activation of Akt and integrin-linked kinase.''; Can J Physiol Pharmacol, 2010 PubMed Europe PMC Scholia
  46. Spinella F, Rosano L, Di Castro V, Nicotra MR, Natali PG, Bagnato A; ''Endothelin-1 decreases gap junctional intercellular communication by inducing phosphorylation of connexin 43 in human ovarian carcinoma cells.''; J Biol Chem, 2003 PubMed Europe PMC Scholia
  47. Lin CC, Hsieh HL, Chi PL, Yang CC, Hsiao LD, Yang CM; ''Upregulation of COX-2/PGE2 by ET-1 mediated through Ca2+-dependent signals in mouse brain microvascular endothelial cells.''; Mol Neurobiol, 2014 PubMed Europe PMC Scholia
  48. Foschi M, Franchi F, Han J, La Villa G, Sorokin A; ''Endothelin-1 induces serine phosphorylation of the adaptor protein p66Shc and its association with 14-3-3 protein in glomerular mesangial cells.''; J Biol Chem, 2001 PubMed Europe PMC Scholia
  49. Mandal A, Shahidullah M, Beimgraben C, Delamere NA; ''The effect of endothelin-1 on Src-family tyrosine kinases and Na,K-ATPase activity in porcine lens epithelium.''; J Cell Physiol, 2011 PubMed Europe PMC Scholia
  50. Cianfrocca R, Tocci P, Semprucci E, Spinella F, Di Castro V, Bagnato A, Rosano L; ''β-Arrestin 1 is required for endothelin-1-induced NF-κB activation in ovarian cancer cells.''; Life Sci, 2014 PubMed Europe PMC Scholia
  51. Bisotto S, Fixman ED; ''Src-family tyrosine kinases, phosphoinositide 3-kinase and Gab1 regulate extracellular signal-regulated kinase 1 activation induced by the type A endothelin-1 G-protein-coupled receptor.''; Biochem J, 2001 PubMed Europe PMC Scholia
  52. Lamers JM, Eskildsen-Helmond YE, Resink AM, de Jonge HW, Bezstarosti K, Sharma HS, van Heugten HA; ''Endothelin-1-induced phospholipase C-beta and D and protein kinase C isoenzyme signaling leading to hypertrophy in rat cardiomyocytes.''; J Cardiovasc Pharmacol, 1995 PubMed Europe PMC Scholia
  53. Tang L, Luo B, Patel RP, Ling Y, Zhang J, Fallon MB; ''Modulation of pulmonary endothelial endothelin B receptor expression and signaling: implications for experimental hepatopulmonary syndrome.''; Am J Physiol Lung Cell Mol Physiol, 2007 PubMed Europe PMC Scholia
  54. Wu X, Zhang T, Bossuyt J, Li X, McKinsey TA, Dedman JR, Olson EN, Chen J, Brown JH, Bers DM; ''Local InsP3-dependent perinuclear Ca2+ signalingin cardiac myocyte excitation-transcription coupling.''; J Clin Invest, 2006 PubMed Europe PMC Scholia
  55. Nemoto S, Taguchi K, Matsumoto T, Kamata K, Kobayashi T; ''Pravastatin normalizes ET-1-induced contraction in the aorta of type 2 diabetic OLETF rats by suppressing the KSR1/ERK complex.''; Am J Physiol Heart Circ Physiol, 2012 PubMed Europe PMC Scholia
  56. Semprucci E, Tocci P, Cianfrocca R, Sestito R, Caprara V, Veglione M, Castro VD, Spadaro F, Ferrandina G, Bagnato A, Rosano L; ''Endothelin A receptor drives invadopodia function and cell motility through the Beta-arrestin/PDZ-RhoGEF pathway in ovarian carcinoma.''; Oncogene, 2016 PubMed Europe PMC Scholia
  57. Cianfrocca R, Tocci P, Rosano L, Caprara V, Sestito R, Di Castro V, Bagnato A; ''Nuclear β-arrestin1 is a critical cofactor of hypoxia-inducible factor-1α signaling in endothelin-1-induced ovarian tumor progression.''; Oncotarget, 2016 PubMed Europe PMC Scholia
  58. Hersch E, Huang J, Grider JR, Murthy KS; ''Gq/G13 signaling by ET-1 in smooth muscle: MYPT1 phosphorylation via ETA and CPI-17 dephosphorylation via ETB.''; Am J Physiol Cell Physiol, 2004 PubMed Europe PMC Scholia
  59. Davies JC, Bain SC, Kanamarlapudi V; ''ADP-ribosylation factor 6 regulates endothelin-1-induced lipolysis in adipocytes.''; Biochem Pharmacol, 2014 PubMed Europe PMC Scholia
  60. Chahdi A, Miller B, Sorokin A; ''Endothelin 1 induces beta 1Pix translocationand Cdc42 activation via protein kinase A-dependent pathway.''; J Biol Chem, 2005 PubMed Europe PMC Scholia
  61. Lima VV, Giachini FR, Carneiro FS, Carvalho MH, Fortes ZB, Webb RC, Tostes RC; ''O-GlcNAcylation contributes to the vascular effects of ET-1 via activation of the RhoA/Rho-kinase pathway.''; Cardiovasc Res, 2011 PubMed Europe PMC Scholia
  62. Hsieh HL, Lin CC, Chan HJ, Yang CM; ''c-Src-dependent EGF receptor transactivation contributes to ET-1-induced COX-2 expression in brain microvascular endothelial cells.''; J Neuroinflammation, 2012 PubMed Europe PMC Scholia
  63. Kim SW, Choi HJ, Lee HJ, He J, Wu Q, Langley RR, Fidler IJ, Kim SJ; ''Role of the endothelin axis in astrocyte- and endothelial cell-mediated chemoprotection of cancer cells.''; Neuro Oncol, 2014 PubMed Europe PMC Scholia
  64. Wu MH, Lo JF, Kuo CH, Lin JA, Lin YM, Chen LM, Tsai FJ, Tsai CH, Huang CY, Tang CH; ''Endothelin-1 promotes MMP-13 production and migration in human chondrosarcoma cells through FAK/PI3K/Akt/mTOR pathways.''; J Cell Physiol, 2012 PubMed Europe PMC Scholia
  65. Lin CC, Lin WN, Hou WC, Hsiao LD, Yang CM; ''Endothelin-1 induces VCAM-1 expression-mediated inflammation via receptor tyrosine kinases and Elk/p300 in human tracheal smooth muscle cells.''; Am J Physiol Lung Cell Mol Physiol, 2015 PubMed Europe PMC Scholia
  66. Rufanova VA, Alexanian A, Wakatsuki T, Lerner A, Sorokin A; ''Pyk2 mediates endothelin-1 signaling via p130Cas/BCAR3 cascade and regulates human glomerular mesangial cell adhesion and spreading.''; J Cell Physiol, 2009 PubMed Europe PMC Scholia
  67. Häuselmann SP, Rosc-Schlüter BI, Lorenz V, Plaisance I, Brink M, Pfister O, Kuster GM; ''β1-Integrin is up-regulated via Rac1-dependent reactive oxygen species as part of the hypertrophic cardiomyocyte response.''; Free Radic Biol Med, 2011 PubMed Europe PMC Scholia
  68. Asada S, Takanami-Ohnishi Y, Zhou J, Hama H, Fukamizu A, Kimura S, Goto K, Kasuya Y; ''Cytodifferentiation enhances Erk activation induced by endothelin-1 in primary cultured astrocytes.''; J Cardiovasc Pharmacol, 2004 PubMed Europe PMC Scholia
  69. Dao HH, Bouvet C, Moreau S, Beaucage P, Larivière R, Servant MJ, de Champlain J, Moreau P; ''Endothelin is a dose-dependent trophic factor and a mitogen in small arteries in vivo.''; Cardiovasc Res, 2006 PubMed Europe PMC Scholia
  70. Rosano L, Cianfrocca R, Masi S, Spinella F, Di Castro V, Biroccio A, Salvati E, Nicotra MR, Natali PG, Bagnato A; ''Beta-arrestin links endothelin A receptor to beta-catenin signaling to induce ovarian cancer cell invasion and metastasis.''; Proc Natl Acad Sci U S A, 2009 PubMed Europe PMC Scholia
  71. Schinelli S, Zanassi P, Paolillo M, Wang H, Feliciello A, Gallo V; ''Stimulation of endothelin B receptors in astrocytes induces cAMP response element-binding protein phosphorylation and c-fos expression via multiple mitogen-activated protein kinase signaling pathways.''; J Neurosci, 2001 PubMed Europe PMC Scholia
  72. Xu H, Zhou Y, Lu C, Ping J, Xu LM; ''Salvianolic acid B lowers portal pressure in cirrhotic rats and attenuates contraction of rat hepatic stellate cells by inhibiting RhoA signaling pathway.''; Lab Invest, 2012 PubMed Europe PMC Scholia
  73. Kawanabe Y, Nozaki K, Hashimoto N, Masaki T; ''Involvement of extracellular Ca2+ influx and epidermal growth factor receptor tyrosine kinase transactivation in endothelin-1-induced arachidonic acid release.''; Br J Pharmacol, 2003 PubMed Europe PMC Scholia
  74. Yang LL, Gros R, Kabir MG, Sadi A, Gotlieb AI, Husain M, Stewart DJ; ''Conditional cardiac overexpression of endothelin-1 induces inflammation and dilated cardiomyopathy in mice.''; Circulation, 2004 PubMed Europe PMC Scholia
  75. Rosano L, Cianfrocca R, Tocci P, Spinella F, Di Castro V, Caprara V, Semprucci E, Ferrandina G, Natali PG, Bagnato A; ''Endothelin A receptor Beta-arrestin signaling to the Wnt pathway renders ovarian cancer cells resistant to chemotherapy.''; Cancer Res, 2014 PubMed Europe PMC Scholia
  76. Cazaubon SM, Ramos-Morales F, Fischer S, Schweighoffer F, Strosberg AD, Couraud PO; ''Endothelin induces tyrosine phosphorylation and GRB2 association of Shc in astrocytes.''; J Biol Chem, 1994 PubMed Europe PMC Scholia
  77. Dlugosz JA, Munk S, Ispanovic E, Goldberg HJ, Whiteside CI; ''Mesangial cell filamentous actin disassembly and hypocontractility in high glucose are mediated by PKC-zeta.''; Am J Physiol Renal Physiol, 2002 PubMed Europe PMC Scholia
  78. Fernandez-Patron C, Zouki C, Whittal R, Chan JS, Davidge ST, Filep JG; ''Matrix metalloproteinases regulate neutrophil-endothelial cell adhesion through generation of endothelin-1[1-32].''; FASEB J, 2001 PubMed Europe PMC Scholia
  79. Imamura T, Ishibashi K, Dalle S, Ugi S, Olefsky JM; ''Endothelin-1-induced GLUT4 translocation is mediated via Galpha(q/11) protein and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes.''; J Biol Chem, 1999 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
118893view16:15, 3 June 2021EgonwCorrected the datasource
116783view09:53, 14 May 2021EweitzModified title
116043view07:18, 2 April 2021EgonwFixed duplicate reference info
115966view11:05, 22 March 2021Finterly
115965view09:39, 22 March 2021FinterlyFixed special characters.
115888view16:24, 19 March 2021Keshav
111629view10:54, 31 August 2020KeshavUpdate
111219view05:26, 25 July 2020Rex D A Bupdated connections and legend
111218view05:17, 25 July 2020Rex D A Bconnections
111217view04:13, 25 July 2020Rex D A Bconnections
111119view07:23, 15 July 2020KeshavModified description
110556view10:25, 18 May 2020Fehrhartfixed weird characters in b-(beta)-arrestin dependant pathway
110555view10:22, 18 May 2020Fehrhartconverted some obvious graphical lines
110522view06:56, 17 May 2020EgonwChanged two more datasources to RefSeq and added a missing Entrez Gene ID
110521view06:51, 17 May 2020Egonw
110004view15:43, 12 April 2020KeshavInteractions
109888view18:46, 3 April 2020KeshavInteractions
109759view18:43, 30 March 2020KeshavOntology Term : 'pulmonary hypertension' added !
109758view18:34, 30 March 2020KeshavOntology Term : 'cystic fibrosis' added !
109757view18:32, 30 March 2020KeshavOntology Term : 'endothelin signaling pathway' added !
109746view13:10, 30 March 2020KeshavReverted to version '15:28, 29 March 2020' by Keshav
109736view08:09, 30 March 2020MadeomugaOntology Term : 'endothelin signaling pathway' added !
109721view15:28, 29 March 2020KeshavIntereactions
109543view07:33, 23 March 2020KeshavNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
Cardiac hypertrophy
ABHD3GeneProduct171586 (Entrez Gene)
ABL1ProteinNP_009297.2 (NCBI Protein)
ACTA2GeneProduct59 (Entrez Gene)
ACTG2GeneProduct72 (Entrez Gene)
ACTR1AGeneProduct10121 (Entrez Gene)
ACTR2GeneProduct10097 (Entrez Gene)
ACTR3GeneProduct10096 (Entrez Gene)
ADAM12GeneProductADAM12
ADAM17GeneProduct6868 (Entrez Gene)
ADAM19GeneProductADAM19
ADIPOQGeneProduct9370 (Entrez Gene)
AKT1ProteinNP_005154.2 (NCBI Protein)
ANXA7GeneProduct310 (Entrez Gene)
ARF6GeneProduct382 (Entrez Gene)
ARHGAP35ProteinNP_004482.4 (NCBI Protein)
ARHGEF11GeneProductARHGEF11
ARHGEF7GeneProduct8874 (Entrez Gene)
ARL6IP5GeneProduct10550 (Entrez Gene)
ARPC4GeneProduct10093 (Entrez Gene)
ARRB1GeneProduct408 (Entrez Gene)
ARRB1GeneProductARRB1
ATF1ProteinNP_005162.1 (NCBI Protein)
ATF2ProteinNP_001871.2 (NCBI Protein)
ATP6V1HGeneProduct51606 (Entrez Gene)
ATRXGeneProduct546 (Entrez Gene)
AXIN1GeneProduct8312 (Entrez Gene)
Actin polymerizationPathway
B3GNT2GeneProduct10678 (Entrez Gene)
BADProtein
BCAR1GeneProduct9564 (Entrez Gene)
BCAR3GeneProduct8412 (Entrez Gene)
BCL2GeneProduct596 (Entrez Gene)
BMI1GeneProduct648 (Entrez Gene)
Blood vessel contraction
Brain inflamation disorders
CALD1GeneProduct800 (Entrez Gene)
CALD1ProteinNP_149129.2 (NCBI Protein)
CALM1GeneProduct801 (Entrez Gene)
CAMK2AProteinNP_057065.2 (NCBI Protein)
CAMK2GProtein5970 (Entrez Gene)
CAPZBGeneProduct832 (Entrez Gene)
CASP8GeneProduct841 (Entrez Gene)
CCL2GeneProduct6347 (Entrez Gene)
CCN2GeneProduct1490 (Entrez Gene)
CCNB1GeneProduct891 (Entrez Gene)
CCND1GeneProduct595 (Entrez Gene)
CCS differentiationPathway
CDC42 GeneProduct998 (Entrez Gene)
CDH1GeneProduct999 (Entrez Gene)
CDH2GeneProduct1000 (Entrez Gene)
CDK2GeneProduct1017 (Entrez Gene)
CDKN1BProteinNP_004055.1 (NCBI Protein)
CFL1ProteinNP_005498.1 (NCBI Protein)
CFL2ProteinNP_068733.1 (NCBI Protein)
CHUKProteinNP_001269.3 (NCBI Protein)
COL1A1GeneProduct1277 (Entrez Gene)
COL1A2GeneProduct1278 (Entrez Gene)
COL1A3GeneProduct1279 (Entrez Gene)
COL1A4GeneProduct1280 (Entrez Gene)
COL4A1GeneProductCOL4A1
COL5A1GeneProductCOL5A1
COL7A1GeneProductCOL7A1
COL9A1GeneProduct1297 (Entrez Gene)
COMPGeneProductCOMP
COX1GeneProduct4512 (Entrez Gene)
COX2GeneProduct4513 (Entrez Gene)
CREB1GeneProductNP_604391.1 (NCBI Protein)
CREBProteinNP_604391.1 (NCBI Protein)
CREG1GeneProduct8804 (Entrez Gene)
CRYZL1GeneProduct9946 (Entrez Gene)
CSF2GeneProduct1437 (Entrez Gene)
CTNNB1GeneProduct1499 (Entrez Gene)
CTNND1GeneProduct1500 (Entrez Gene)
CX3CL1GeneProduct6376 (Entrez Gene)
CXCL1GeneProduct2919 (Entrez Gene)
CXCL8GeneProduct3576 (Entrez Gene)
Cell invasion
Cell invasion
Cell migration
Cell survival

and

angiogenesis		Pathway
Cellular proliferation, migration and contraction in colon cancer adjacent fibroblasts
Chemo protection
CytoplasmPathway
Cytoskeletal polymerisation
DAG1Protein
DAZAP2GeneProduct9802 (Entrez Gene)
DLATGeneProduct1737 (Entrez Gene)
DNAJC10GeneProduct54431 (Entrez Gene)
DNAJC12GeneProduct56521 (Entrez Gene)
E2F3GeneProduct1871 (Entrez Gene)
ECM contraction
EDN1Protein1906 (Entrez Gene)
EDN3Protein1908 (Entrez Gene)
EDNRAProtein1909 (Entrez Gene)
EDNRBProtein1910 (Entrez Gene)
EGFRProtein1956 (Entrez Gene)
EGR1GeneProduct1958 (Entrez Gene)
EIF2BProteinNP_001305894.1 (NCBI Protein)
EIF5BGeneProduct9669 (Entrez Gene)
ELK1ProteinNP_005220.2 (NCBI Protein)
EMC1GeneProduct23065 (Entrez Gene)
EP2Protein5732 (Entrez Gene)
EP300ProteinNP_001420.2 (NCBI Protein)
EP4Protein5734 (Entrez Gene)
EPHA2GeneProduct1969 (Entrez Gene)
EZRGeneProduct7430 (Entrez Gene)
Epithelial to mesenchymal transition (EMT)
FASTKD1GeneProduct79675 (Entrez Gene)
FGF2GeneProductFGF2
FHL2GeneProduct2274 (Entrez Gene)
FLI1ProteinNP_002008.2 (NCBI Protein)
FLNBGeneProduct2317 (Entrez Gene)
FLNCGeneProduct2318 (Entrez Gene)
FNDC1 GeneProduct84624 (Entrez Gene)
FNDC3BGeneProduct64778 (Entrez Gene)
FOSGeneProduct2353 (Entrez Gene)
FOXK2GeneProduct3607 (Entrez Gene)
FOXO3ProteinNP_001446.1 (NCBI Protein)
FYNProteinNP_002028.1 (NCBI Protein)
G-protein dependentPathway
GAB1ProteinNP_997006.1 (RefSeq)
GALNT1GeneProduct2589 (Entrez Gene)
GATA4GeneProduct2626 (Entrez Gene)
GATA4ProteinNP_001295022.1 (NCBI Protein)
GGA2GeneProduct23062 (Entrez Gene)
GJA5GeneProduct2702 (Entrez Gene)
GJC1GeneProduct10052 (Entrez Gene)
GLSGeneProduct2744 (Entrez Gene)
GNA12GeneProduct2768 (Entrez Gene)
GNA13GeneProduct10672 (Entrez Gene)
GNAQGeneProduct10672 (Entrez Gene)
GNASGeneProduct2778 (Entrez Gene)
GOLGB1GeneProduct2804 (Entrez Gene)
GRB2 GeneProduct2885 (Entrez Gene)
GSK3BGeneProduct2932 (Entrez Gene)
GSNGeneProduct2934 (Entrez Gene)
GSTA5GeneProduct221357 (Entrez Gene)
GULP1GeneProduct51454 (Entrez Gene)
HDAC5GeneProduct10014 (Entrez Gene)
HIF1AGeneProduct3091 (Entrez Gene)
HLA-AGeneProduct3105 (Entrez Gene)
HOPXGeneProduct84525 (Entrez Gene)
HSPB1ProteinNP_001531.1 (NCBI Protein)
HTATSF1GeneProduct27336 (Entrez Gene)
HypoxiaPathway
IGFBP4GeneProduct3487 (Entrez Gene)
IGFBP5GeneProduct3488 (Entrez Gene)
IKBKBProteinNP_001547.1 (NCBI Protein)
IL11GeneProduct3589 (Entrez Gene)
IL1BGeneProduct3553 (Entrez Gene)
IL6GeneProduct3569 (Entrez Gene)
ILKGeneProduct3611 (Entrez Gene)
IPK1GeneProduct
IRS1 Protein
IRX4GeneProduct50805 (Entrez Gene)
ISCA1GeneProduct81689 (Entrez Gene)
ITGA2GeneProduct3673 (Entrez Gene)
ITGA2GeneProductITGA2
ITGA5GeneProductITGA5
ITGB1GeneProduct3688 (Entrez Gene)
ITGB1BP1GeneProduct9270 (Entrez Gene)
ITGB3GeneProduct3690 (Entrez Gene)
ITGB3GeneProductITGB3
InflammationPathway
Invasion

and

metastasis
JAK1ProteinNP_002218.2 (NCBI Protein)
JUNGeneProduct3725 (Entrez Gene)
JUNProteinNP_002219.1 (NCBI Protein)
KCNK3 GeneProduct3777 (Entrez Gene)
KDM5BGeneProduct10765 (Entrez Gene)
KLHL20GeneProduct27252 (Entrez Gene)
KRAS GeneProduct3845 (Entrez Gene)
KSR1ProteinNP_055053.1 (RefSeq)
LEPRGeneProduct3953 (Entrez Gene)
LIMKProteinNP_002305.1 (NCBI Protein)
Lung fibrosisPathway
MAP2K1GeneProduct5604 (Entrez Gene)
MAP2K2 ProteinNP_109587.1 (RefSeq)
MAP3K2GeneProduct10746 (Entrez Gene)
MAPK14ProteinNP_001306.1 (NCBI Protein)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
MAPK8ProteinNP_001310259.1 (NCBI Protein)
MAPK9ProteinNP_002743.3 (NCBI Protein)
MARCKSGeneProduct4082 (Entrez Gene)
MCAMGeneProduct4162 (Entrez Gene)
MED12GeneProduct9968 (Entrez Gene)
MEF2AGeneProduct4205 (Entrez Gene)
MINK1GeneProduct50488 (Entrez Gene)
MLC ProteinNP_055981.1 (NCBI Protein)
MLCKGeneProduct4638 (Entrez Gene)
MMP13GeneProduct4322 (Entrez Gene)
MMP14GeneProduct4323 (Entrez Gene)
MMP1GeneProductMMP1
MMP2GeneProduct4313 (Entrez Gene)
MMP3GeneProductMMP3
MMP9GeneProduct4318 (Entrez Gene)
MPP5GeneProduct64398 (Entrez Gene)
MPPED2GeneProduct744 (Entrez Gene)
MSNGeneProduct4478 (Entrez Gene)
MTORProteinNP_004949.1 (NCBI Protein)
MYBPC3GeneProduct4607 (Entrez Gene)
MYH11Protein4629 (Entrez Gene)
MYL12BProteinNP_001138416.1 (NCBI Protein)
MYO1BGeneProduct4430 (Entrez Gene)
Metastasis

and tumor

progression
NAA16GeneProduct79612 (Entrez Gene)
NAA50GeneProduct80218 (Entrez Gene)
NFATC1ProteinNP_001265598.1 (NCBI Protein)
NFKB1Protein4790 (Entrez Gene)
NFKBIAProtein4792 (Entrez Gene)
NKX2-5GeneProduct1482 (Entrez Gene)
NO accumulationPathway
NOL8GeneProduct55035 (Entrez Gene)
NOS3GeneProduct4846 (Entrez Gene)
NOS3ProteinNP_000594.2 (NCBI Protein)
NOX5GeneProduct79400 (Entrez Gene)
NPPAGeneProduct4878 (Entrez Gene)
NPPBGeneProduct4879 (Entrez Gene)
NQO1GeneProduct1728 (Entrez Gene)
NucleusPathway
P4HBGeneProduct5034 (Entrez Gene)
PAK1GeneProduct5058 (Entrez Gene)
PIK3CAGeneProduct5290 (Entrez Gene)
PKCGeneProduct5566 (Entrez Gene)
PLA2Protein
PLCB1GeneProduct23236 (Entrez Gene)
PLOD2GeneProductPLOD2
PPP1R12AGeneProduct4659 (Entrez Gene)
PPP1R12AProteinNP_002471.1 (NCBI Protein)
PPP1R14AProtein
PPP3CAGeneProduct5530 (Entrez Gene)
PRKACAGeneProduct5566 (Entrez Gene)
PRKCAGeneProduct5578 (Entrez Gene)
PTGS2GeneProduct5743 (Entrez Gene)
PTK2Protein
PTK2BGeneProduct2185 (Entrez Gene)
PXNGeneProduct5829 (Entrez Gene)
Pulmonary hypertensionPathway
RAB5CGeneProduct5878 (Entrez Gene)
RAC1 GeneProduct5879 (Entrez Gene)
RAC1GeneProduct5879 (Entrez Gene)
RAF1 GeneProduct5894 (Entrez Gene)
RAP1GAP GeneProduct5909 (Entrez Gene)
RDXGeneProduct5962 (Entrez Gene)
RELAProtein5970 (Entrez Gene)
RGS3GeneProduct5998 (Entrez Gene)
RHOA GeneProduct387 (Entrez Gene)
RHOCProtein389 (Entrez Gene)
ROCK1 GeneProduct6093 (Entrez Gene)
RPS6KA2ProteinNP_001305865.1 (NCBI Protein)
RPS6KA3ProteinNP_004577.1 (NCBI Protein)
RPS6KB1ProteinNP_003152.1 (NCBI Protein)
RPS6ProteinNP_001001.2 (NCBI Protein)
RUNX1GeneProduct861 (Entrez Gene)
Renal fibrosis
SDC1GeneProductSDC1
SHC GeneProduct6464 (Entrez Gene)
SHC1GeneProduct6464 (Entrez Gene)
SMAD5GeneProduct4090 (Entrez Gene)
SNAI1GeneProduct6615 (Entrez Gene)
SOSGeneProduct6654 (Entrez Gene)
SP4GeneProduct6671 (Entrez Gene)
SRCGeneProduct6714 (Entrez Gene)
SREGeneProductserum response element (Other)
SSH1GeneProduct54434 (Entrez Gene)
STAT3ProteinNP_644805.1 (NCBI Protein)
STOMGeneProduct2040 (Entrez Gene)
Smooth muscle differentiationPathway
TAGLN2GeneProduct8407 (Entrez Gene)
TCF4GeneProduct6925 (Entrez Gene)
THBS1GeneProductTHBS1
TIMP3 GeneProductTIMP3
TNFGeneProduct7124 (Entrez Gene)
TNS1GeneProduct7145 (Entrez Gene)
TPM1GeneProduct7168 (Entrez Gene)
TPM4GeneProduct7171 (Entrez Gene)
TRAFD1GeneProduct10906 (Entrez Gene)
TRIOBPGeneProduct11078 (Entrez Gene)
TWIST1GeneProduct17291 (Entrez Gene)
VCAM1GeneProduct7412 (Entrez Gene)
VCANGeneProductVCAN
VEGFAGeneProduct7422 (Entrez Gene)
VIL1GeneProduct7429 (Entrez Gene)
VIMGeneProduct7431 (Entrez Gene)
WIPF1GeneProduct7456 (Entrez Gene)
WNK1GeneProduct65125 (Entrez Gene)
WWTR1GeneProduct25937 (Entrez Gene)
YAP1GeneProduct10413 (Entrez Gene)
YWHAQGeneProduct10971 (Entrez Gene)
ZFYVE16GeneProduct9765 (Entrez Gene)
ZNF131GeneProduct7690 (Entrez Gene)
ZNF136GeneProduct7695 (Entrez Gene)
b-arrestin dependentPathway

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP4857"
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