Adrenomedullin signaling pathway
Adrenomedullin (AM) is a peptide initially isolated from tumors (pheochromocytoma) of the adrenal gland. It consists of 52 amino acid residues with one intracellular disulfide bond and is a member of the calcitonin gene-related peptide (CGRP) family. It is produced by a great number of different cell types, in all tissues of the body, with the possible exception of the thyroid and thymus, and acts in many systems including the cardiovascular, renal, endocrine, reproductive, immune, nervous and musculoskeletal systems.The synthesis of AM can be influenced by physical factors such as shear stress, ventricular wall stress and hypoxia, and humoral factors such as cytokines. Inflammatory cytokines including tumor necrosis factor TNF-α, TNF-β, interleukin IL-1 and lipopolysacccharide (LPS) stimulate the synthesis and secretion of AM in endothelial cells and vascular smooth muscle cells (VSMCs) which gives this peptide a significant role in sepsis and inflammation...
Pathway Summary
Adrenomedullin (AM) is a peptide initially isolated from tumors (pheochromocytoma) of the adrenal gland. It consists of 52 amino acid residues with one intracellular disulfide bond and is a member of the calcitonin gene-related peptide (CGRP) family. It is produced by a great number of different cell types, in all tissues of the body, with the possible exception of the thyroid and thymus, and acts in many systems including the cardiovascular, renal, endocrine, reproductive, immune, nervous and musculoskeletal systems.The synthesis of AM can be influenced by physical factors such as shear stress, ventricular wall stress and hypoxia, and humoral factors such as cytokines. Inflammatory cytokines including tumor necrosis factor TNF-α, TNF-β, interleukin IL-1 and lipopolysacccharide (LPS) stimulate the synthesis and secretion of AM in endothelial cells and vascular smooth muscle cells (VSMCs) which gives this peptide a significant role in sepsis and inflammation.AM mediates its action through complexes composed of calcitonin receptor-like receptor (CL) combined with receptor activity modifying proteins (RAMP2 and RAMP3). RAMPs are single-membrane domain proteins that assist with transportation of CL to the cell surface and also interaction with G proteins.The signal transduction pathways activated by AM vary between species, organs, tissues, and cells. Biological action of AM was initially considered to be mediated solely via cAMP/PKA pathway, but subsequent studies have revealed that pleiotropic effects of AM are mediated through several additional intracellular signal transduction pathways, such as ERK/MAPK, PI3K/AKT, and NO/cGMP/PKG. The vasodilatory and hypotensive actions of AM are mediated mainly by a direct action on VSMCs to increase intracellular cAMP, and also by activation of PI3K/AKT pathway in endothelial cells to stimulate NO release. The MAKP/ERK1/2 pathway is involved in the angiogenic action of AM in endothelial cells.Many studies that show an association between AM expression and cancer. AM can stimulate cell growth and inhibit apoptosis in a variety of tumor cells, including pancreatic adenocarcinoma, prostate cancer, ovarian cancer, osteosarcoma, renal carcinoma, breast cancer, colorectal cancer and hepatocellular carcinoma. Therefore, new therapies based on blockade of the AM autocrine/paracrine system have been developed and some of them are effective in animal models.
Adrenomedullin signaling pathway Genes list
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ADCY1adenylate cyclase 1 ADCY10adenylate cyclase 10 ADCY2adenylate cyclase 2 ADCY3adenylate cyclase 3 ADCY4adenylate cyclase 4 ADCY5adenylate cyclase 5 ADCY6adenylate cyclase 6 ADCY7adenylate cyclase 7 ADCY8adenylate cyclase 8 ADCY9adenylate cyclase 9 ADMadrenomedullin AKT1AKT serine/threonine kinase 1 AKT2AKT serine/threonine kinase 2 AKT3AKT serine/threonine kinase 3 ARAFA-Raf proto-oncogene, serine/threonine kinase ARNTaryl hydrocarbon receptor nuclear translocator BADBCL2 associated agonist of cell death BAXBCL2 associated X, apoptosis regulator BCL2BCL2 apoptosis regulator BRAFB-Raf proto-oncogene, serine/threonine kinase CALCRLcalcitonin receptor like receptor CALML5calmodulin like 5 CAMPcathelicidin antimicrobial peptide CASP3caspase 3 CEBPBCCAAT enhancer binding protein beta CFHcomplement factor H CRCPCGRP receptor component CSKC-terminal Src kinase CTHcystathionine gamma-lyase ELK1ETS transcription factor ELK1 ERASES cell expressed Ras FOSFos proto-oncogene, AP-1 transcription factor subunit GAD1glutamate decarboxylase 1 GASTgastrin GNA11G protein subunit alpha 11 GNA14G protein subunit alpha 14 GNA15G protein subunit alpha 15 GNAQG protein subunit alpha q GPR182G protein-coupled receptor 182 GPR37G protein-coupled receptor 37 GRB2growth factor receptor bound protein 2 GSK3Aglycogen synthase kinase 3 alpha GSK3Bglycogen synthase kinase 3 beta GUCY1A1guanylate cyclase 1 soluble subunit alpha 1 GUCY1A2guanylate cyclase 1 soluble subunit alpha 2 GUCY1B1guanylate cyclase 1 soluble subunit beta 1 GUCY1B2guanylate cyclase 1 soluble subunit beta 2 (pseudogene) GUCY2Cguanylate cyclase 2C GUCY2Dguanylate cyclase 2D, retinal GUCY2Fguanylate cyclase 2F, retinal H2BW2H2B.W histone 2 HIF1Ahypoxia inducible factor 1 subunit alpha HRASHRas proto-oncogene, GTPase IL18interleukin 18 IL1Ainterleukin 1 alpha IL1Binterleukin 1 beta IL1F10interleukin 1 family member 10 IL1RNinterleukin 1 receptor antagonist IL33interleukin 33 IL36Ainterleukin 36 alpha IL36Binterleukin 36 beta IL36Ginterleukin 36 gamma IL36RNinterleukin 36 receptor antagonist IL37interleukin 37 ITPR1inositol 1,4,5-trisphosphate receptor type 1 ITPR2inositol 1,4,5-trisphosphate receptor type 2 ITPR3inositol 1,4,5-trisphosphate receptor type 3 KCNH2potassium voltage-gated channel subfamily H member 2 KCNN1potassium calcium-activated channel subfamily N member 1 KCNN2potassium calcium-activated channel subfamily N member 2 KCNN3potassium calcium-activated channel subfamily N member 3 KCNN4potassium calcium-activated channel subfamily N member 4 KCNQ2potassium voltage-gated channel subfamily Q member 2 KCNQ3potassium voltage-gated channel subfamily Q member 3 KRASKRAS proto-oncogene, GTPase LTAlymphotoxin alpha MAP2K1mitogen-activated protein kinase kinase 1 MAP2K2mitogen-activated protein kinase kinase 2 MAP2K3mitogen-activated protein kinase kinase 3 MAP2K4mitogen-activated protein kinase kinase 4 MAP2K5mitogen-activated protein kinase kinase 5 MAP2K6mitogen-activated protein kinase kinase 6 MAP2K7mitogen-activated protein kinase kinase 7 MAPK1mitogen-activated protein kinase 1 MAPK10mitogen-activated protein kinase 10 MAPK11mitogen-activated protein kinase 11 MAPK12mitogen-activated protein kinase 12 MAPK13mitogen-activated protein kinase 13 MAPK14mitogen-activated protein kinase 14 MAPK15mitogen-activated protein kinase 15 MAPK3mitogen-activated protein kinase 3 MAPK4mitogen-activated protein kinase 4 MAPK6mitogen-activated protein kinase 6 MAPK7mitogen-activated protein kinase 7 MAPK8mitogen-activated protein kinase 8 MAPK9mitogen-activated protein kinase 9 MATKmegakaryocyte-associated tyrosine kinase MAXMYC associated factor X MMP2matrix metallopeptidase 2 MRASmuscle RAS oncogene homolog MYLKmyosin light chain kinase MYLK2myosin light chain kinase 2 MYLK3myosin light chain kinase 3 NFKB1nuclear factor kappa B subunit 1 NFKB2nuclear factor kappa B subunit 2 NOS3nitric oxide synthase 3 NOTUMnotum, palmitoleoyl-protein carboxylesterase NPR1natriuretic peptide receptor 1 NPR2natriuretic peptide receptor 2 NPR3natriuretic peptide receptor 3 NRASNRAS proto-oncogene, GTPase NT5C5', 3'-nucleotidase, cytosolic PDIA3protein disulfide isomerase family A member 3 PIK3C2Aphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha PIK3C2Bphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta PIK3C2Gphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma PIK3C3phosphatidylinositol 3-kinase catalytic subunit type 3 PIK3CAphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha PIK3CBphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta PIK3CGphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma PIK3R1phosphoinositide-3-kinase regulatory subunit 1 PIK3R2phosphoinositide-3-kinase regulatory subunit 2 PIK3R3phosphoinositide-3-kinase regulatory subunit 3 PIK3R4phosphoinositide-3-kinase regulatory subunit 4 PIK3R5phosphoinositide-3-kinase regulatory subunit 5 PIK3R6phosphoinositide-3-kinase regulatory subunit 6 PLCB1phospholipase C beta 1 PLCB2phospholipase C beta 2 PLCB3phospholipase C beta 3 PLCB4phospholipase C beta 4 PLCD1phospholipase C delta 1 PLCD3phospholipase C delta 3 PLCD4phospholipase C delta 4 PLCE1phospholipase C epsilon 1 PLCG1phospholipase C gamma 1 PLCG2phospholipase C gamma 2 PLCH1phospholipase C eta 1 PLCH2phospholipase C eta 2 PLCL1phospholipase C like 1 (inactive) PLCL2phospholipase C like 2 PLCZ1phospholipase C zeta 1 PPARGperoxisome proliferator activated receptor gamma PRKACAprotein kinase cAMP-activated catalytic subunit alpha PRKACBprotein kinase cAMP-activated catalytic subunit beta PRKACGprotein kinase cAMP-activated catalytic subunit gamma PRKAG1protein kinase AMP-activated non-catalytic subunit gamma 1 PRKAG2protein kinase AMP-activated non-catalytic subunit gamma 2 PRKAR1Aprotein kinase cAMP-dependent type I regulatory subunit alpha PRKAR1Bprotein kinase cAMP-dependent type I regulatory subunit beta PRKAR2Aprotein kinase cAMP-dependent type II regulatory subunit alpha PRKAR2Bprotein kinase cAMP-dependent type II regulatory subunit beta PRKG1protein kinase cGMP-dependent 1 PRKG2protein kinase cGMP-dependent 2 PTK2protein tyrosine kinase 2 PTK2Bprotein tyrosine kinase 2 beta RAF1Raf-1 proto-oncogene, serine/threonine kinase RALARAS like proto-oncogene A RALBRAS like proto-oncogene B RAMP2receptor activity modifying protein 2 RAMP3receptor activity modifying protein 3 RAP1ARAP1A, member of RAS oncogene family RAP1BRAP1B, member of RAS oncogene family RAP2ARAP2A, member of RAS oncogene family RAP2BRAP2B, member of RAS oncogene family RASD1ras related dexamethasone induced 1 RASD2RASD family member 2 RELREL proto-oncogene, NF-kB subunit RELARELA proto-oncogene, NF-kB subunit RELBRELB proto-oncogene, NF-kB subunit RRASRAS related RRAS2RAS related 2 RXRAretinoid X receptor alpha RXRBretinoid X receptor beta RXRGretinoid X receptor gamma SHC1SHC adaptor protein 1 SHC2SHC adaptor protein 2 SHC3SHC adaptor protein 3 SHESrc homology 2 domain containing E SHFSrc homology 2 domain containing F SLC39A7solute carrier family 39 member 7 SMARCC2SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 2 SOS1SOS Ras/Rac guanine nucleotide exchange factor 1 SOS2SOS Ras/Rho guanine nucleotide exchange factor 2 SOX15SRY-box transcription factor 15 TFAP2Atranscription factor AP-2 alpha TFAP2Btranscription factor AP-2 beta TFAP2Ctranscription factor AP-2 gamma TFAP2Dtranscription factor AP-2 delta TFAP2Etranscription factor AP-2 epsilon TNFtumor necrosis factor TTNtitin
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