Panther Pathway: P00019 Endothelin (ET) is formed via three proteolytic cleavages. The four ETs bind to the two ET receptors (ET-R A and B), which are 7 transmembrane-spanning, G-protein coupled receptors. ET-R A and B activation multiple downstream pathways, including PKC-ERK, PI 3K-Akt, and cPLA2. The results are release of NO and prostacyclins (PGI2), mitogenesis, and differentiation primarily effecting endothelial and vascular smooth muscle cells. Medline=10065337 Medline=10443571 Medline=12839262 PMID: 10065337 PMID: 10443571 PMID: 12839262 4.0 s57 PROTEIN p1 s57 PROTEIN p20 s58 PROTEIN p1 s58 PROTEIN p8 SQUARE_CLOSEUP_NORTH OVAL inactive active inactive active inactive inactive active inactive inactive inactive active active inactive inactive inactive inactive active active active active active inactive active inactive active inactive inactive inactive active inactive active active inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive inactive inactive inactive active active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active Corbit Kevin SRI International ER cytoplasm Long Name: Furin Synonym: PACE,SPC1 Accession: P00575 inside PROTEIN p6 Long Name: Endothelin 1, 2, 3, and 4 Synonym: EDN1,EDN2,EDN3,EDN4,VIC,Vasoactive instestinal contractor peptide Accession: P00588 inside PROTEIN p8 Long Name: signal peptidase Synonym: Synonym not specified Accession: P00573 inside PROTEIN p9 Long Name: Endothelin-coverting enzyme 1, 2, and 3 Synonym: Synonym not specified Accession: P00585 inside PROTEIN p10 Long Name: guanine nucleotide binding protein q polypeptide Synonym: G-protein q Accession: P00586 inside PROTEIN p11 Long Name: Long Name: calcium ion Synonym: Synonym not specified Accession: U05188 inside ION Ca_super_2_plus Long Name: diacylglycerol Synonym: Synonym not specified Accession: S01656 inside SIMPLE_MOLECULE DAG Long Name: protein kinase c Synonym: Synonym not specified Accession: P00568 inside PROTEIN p19 Long Name: phosphatidylinositol 3-kinase Synonym: 5-bisphosphate 3-kinase,Phosphatidylinositol-4 Accession: P00577 inside PROTEIN p21 Long Name: endothelial cell nitric oxide synthase Synonym: nitric oxide synthase 3 Accession: P00578 inside PROTEIN p25 Long Name: endothelial cell nitric oxide synthase Synonym: nitric oxide synthase 3 Accession: P00578 inside PROTEIN p25 Long Name: adenosine-3'-5'-cyclic monophosphate Synonym: Synonym not specified Accession: S01662 inside SIMPLE_MOLECULE cAMP Long Name: extracellular signal-regulated kinase Synonym: MAPK,Mitogen-activated protein kinase,mitogen-activated protein kinase,p42/44,pp42/44 Accession: P00566 inside PROTEIN p22 Long Name: adenosine-3'-5'-cyclic monophosphate -dependent kinase Synonym: protein kinase A Accession: P00570 inside PROTEIN p26 Long Name: L-arginine Synonym: Synonym not specified Accession: S01654 inside SIMPLE_MOLECULE L-Arg Long Name: L-citrulline Synonym: Synonym not specified Accession: U02235 inside ION L-Cit Long Name: Nitric oxide Synonym: Synonym not specified Accession: U02231 inside ION NO Long Name: guanylate cyclase Synonym: D2Mgh17,GTP pyrophosphate - lyase,guanylyl cyclase Accession: P00581 inside PROTEIN p27 Long Name: guanosine-3'-5'-cyclic monophosphate Synonym: Synonym not specified Accession: S01655 inside SIMPLE_MOLECULE cGMP Long Name: protein kinase, cGMP-dependent Synonym: SERINE/THREONINE-PROTEIN KINASE PKNG,STPK G,guanosine-3'-5'-cyclic monophosphate-dependent kinase,protein kinase G Accession: P00567 inside PROTEIN p28 Long Name: arachidonic acid Synonym: Synonym not specified Accession: S01657 inside SIMPLE_MOLECULE AA Long Name: glycophospholipid Synonym: Synonym not specified Accession: U02237 transmembrane ION GPL Long Name: lysophospholipid Synonym: Synonym not specified Accession: U02234 inside ION LPL Long Name: inositol 1,4,5-triphosphate Synonym: Synonym not specified Accession: S01661 inside SIMPLE_MOLECULE IP_sub_3 Long Name: Pre-pro endothelin 1, 2, 3, and 4 Synonym: Synonym not specified Accession: P00576 inside PROTEIN p13 Long Name: Pro endothelin 1, 2, 3, and 4 Synonym: Synonym not specified Accession: P00571 inside PROTEIN p14 Long Name: Big endothelin 1, 2, 3, and 4 Synonym: Synonym not specified Accession: P00574 inside PROTEIN p15 Long Name: stimulatory G protein Synonym: guanine nucleotide binding protein s polypeptide Accession: P00584 inside PROTEIN p20 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05185 Heterodimer Member Info: ET-RA/B#PROTEIN#endothelin receptor A, B#P00580##;Gs#PROTEIN#stimulatory G protein#P00584#guanine nucleotide binding protein s polypeptide# transmembrane COMPLEX Complex_br_(ET_minus_R_sub_A_slash_B_endsub/G_sub_s) Long Name: Long Name: endothelin receptor A, B Synonym: Synonym not specified Accession: U05186 Heterodimer Member Info: ET-RA/B#PROTEIN#endothelin receptor A, B#P00580##;ET1-4#PROTEIN#Endothelin 1, 2, 3, and 4#P00588#EDN1|EDN2|EDN3|EDN4|VIC|Vasoactive instestinal contractor peptide# transmembrane COMPLEX Complex_br_(ET_minus_R_sub_A_slash_B_endsub/ET1_minus_4) Long Name: GTP Synonym: Synonym not specified Accession: S01659 inside SIMPLE_MOLECULE GTP Long Name: ATP Synonym: Synonym not specified Accession: S01658 inside SIMPLE_MOLECULE ATP Long Name: smooth muscle cell contraction Synonym: Synonym not specified Accession: U02238 inside PHENOTYPE smooth muscle cell_br_contraction Long Name: Long Name: vaso- relaxation Synonym: Synonym not specified Accession: U05187 inside PHENOTYPE vaso_minus__br_relaxation Long Name: phosphatidyl-inositol 4,5 bisphosphate Synonym: Synonym not specified Accession: S01663 inside SIMPLE_MOLECULE PIP_sub_2 Long Name: inositol 1,4,5-triphosphate receptor Synonym: Synonym not specified Accession: P00590 transmembrane PROTEIN p31 Long Name: extracellular signal-regulated kinase Synonym: MAPK,Mitogen-activated protein kinase,mitogen-activated protein kinase,p42/44,pp42/44 Accession: P00566 inside PROTEIN p22 Long Name: serine/threonine Raf-1 protein kinase Synonym: MAP kinase kinase kinase,c-Raf Accession: P00587 inside PROTEIN p34 Long Name: serine/threonine Raf-1 protein kinase Synonym: MAP kinase kinase kinase,c-Raf Accession: P00587 inside PROTEIN p34 Long Name: MAP/ERK kinase Synonym: Dual specificity mitogen-activated protein kinase kinase,ERK activator kinase,MAP kinase kinase Accession: P00572 inside PROTEIN p33 Long Name: MAP/ERK kinase Synonym: Dual specificity mitogen-activated protein kinase kinase,ERK activator kinase,MAP kinase kinase Accession: P00572 inside PROTEIN p33 Long Name: mitogenesis Synonym: Synonym not specified Accession: U02232 inside PHENOTYPE mitogenesis Long Name: cyclooxygenase-2 Synonym: Synonym not specified Accession: P00582 inside PROTEIN p35 Long Name: prostaglandin I2 Synonym: Synonym not specified Accession: S01660 inside SIMPLE_MOLECULE PGI_sub_2 Long Name: PLCbeta Synonym: Synonym not specified Accession: P00591 inside PROTEIN p17 Long Name: Thymoma viral proto-oncogene Synonym: PKB,RAC protein kinase,protein kinase B Accession: P00589 inside PROTEIN p23 Long Name: Thymoma viral proto-oncogene Synonym: PKB,RAC protein kinase,protein kinase B Accession: P00589 inside PROTEIN p23 Long Name: Long Name: calcium ion Synonym: Synonym not specified Accession: U05188 inside ION Ca_super_2_plus Long Name: ? Synonym: Synonym not specified Accession: P00592 inside PROTEIN p36 Long Name: NSCC Synonym: Synonym not specified Accession: P00579 transmembrane PROTEIN p16 Long Name: Cytosolic phospholipase A2 Synonym: Lysophospholipase,Phosphatidylcholine 2-acylhydrolase Accession: P00583 innerSurface PROTEIN p29 Long Name: Cytosolic phospholipase A2 Synonym: Lysophospholipase,Phosphatidylcholine 2-acylhydrolase Accession: P00583 inside PROTEIN p29 Long Name: 3',5'-cyclic AMP synthetase Synonym: AH-related protein,ATP pyrophosphate-lyase,adenylyl cyclase Accession: P00569 innerSurface PROTEIN p24 STATE_TRANSITION a35 a36 a32 DISSOCIATION 0.0031152647975076775,0.5368784395454091 a39 a40 a41 a36 DISSOCIATION 0.23676241918323981,0.19674277764138282 a47 a46 a48 a45 STATE_TRANSITION a59 a33 a62 HETERODIMER_ASSOCIATION 0.5216886512828225,-0.0021950128172814054 0.44321392727316633,0.32364235572505695 a8 a65 a66 a62 STATE_TRANSITION a67 a30 a62 STATE_TRANSITION a69 a42 a41 STATE_TRANSITION a71 a43 a42 STATE_TRANSITION a72 a44 a43 STATE_TRANSITION a74 a37 a33 STATE_TRANSITION a73 a38 a37 INHIBITION a41 a75 DISSOCIATION 0.594117647058825,6.217248937900877E-15 -0.010814249363869877,0.508269720101783 a78 a25 a26 a17 STATE_TRANSITION 0.3296589784471493,5.7728300164150426E-5 a79 a28 a25 a23 STATE_TRANSITION a82 a81 a26 STATE_TRANSITION a83 a45 a24 a31 STATE_TRANSITION a84 a31 a90 STATE_TRANSITION a88 a89 a28 STATE_TRANSITION a87 a90 a89 STATE_TRANSITION a46 a93 a92 STATE_TRANSITION a95 a17 a11 STATE_TRANSITION a68 a32 a30 STATE_TRANSITION a96 a11 a66 STATE_TRANSITION a97 a16 a66 TRANSPORT a98 a24 a81 TRANSPORT 0.36223812742795636,-3.176865586862476E-5 a99 a23 a24 a16 TRUNCATION -0.03183068866412997,0.5490369728619668 a13 a100 a14 a9 TRUNCATION 0.009576377901353128,0.49596924234537443 a14 a102 a15 a6 TRUNCATION 0.006515252998843257,0.4648967910856717 a15 a101 a8 a10 MODULATION a31 a91 PHYSICAL_STIMULATION a38 a75 PHYSICAL_STIMULATION a44 a76 PHYSICAL_STIMULATION a93 a76