KEGG   PATHWAY: etf04919
Entry
etf04919                    Pathway                                
Name
Thyroid hormone signaling pathway - Echinops telfairi (small Madagascar hedgehog)
Description
The thyroid hormones (THs) are important regulators of growth, development and metabolism. The action of TH is mainly mediated by T3 (3,5,3'-triiodo-L-thyronine). Thyroid hormones, L-thyroxine (T4) and T3 enter the cell through transporter proteins. Although the major form of TH in the blood is T4, it is converted to the more active hormone T3 within cells. T3 binds to nuclear thyroid hormone receptors (TRs), which functions as a ligand-dependent transcription factor and controls the expression of target genes (genomic action). Nongenomic mechanisms of action is initiated at the integrin receptor. The plasma membrane alpha(v)beta(3)-integrin has distinct binding sites for T3 and T4. One binding site binds only T3 and activates the phosphatidylinositol 3-kinase (PI3K) pathway. The other binding site binds both T3 and T4 and activates the ERK1/2 MAP kinase pathway.
Class
Organismal Systems; Endocrine system
Pathway map
etf04919  Thyroid hormone signaling pathway
etf04919

Other DBs
GO: 0002154
Organism
Echinops telfairi (small Madagascar hedgehog) [GN:etf]
Gene
101649991  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101645802  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
101643277  ITGAV; integrin alpha-V [KO:K06487]
101653361  ITGB3; integrin beta-3 [KO:K06493]
101663997  HRAS; GTPase HRas isoform X1 [KO:K02833]
101639926  KRAS; GTPase KRas isoform X3 [KO:K07827]
101649328  GTPase NRas-like [KO:K07828]
101653520  NRAS; GTPase NRas [KO:K07828]
101656360  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X3 [KO:K04366] [EC:2.7.11.1]
101650474  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101643986  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101648971  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101661786  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101650838  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101647784  LOW QUALITY PROTEIN: cellular tumor antigen p53-like [KO:K04451]
101656530  TP53; cellular tumor antigen p53 [KO:K04451]
101650948  ESR1; estrogen receptor [KO:K08550]
101655865  THRB; thyroid hormone receptor beta isoform X1 [KO:K08362]
101650558  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
101639140  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
101664320  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
101664236  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
101652123  HDAC3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
101663528  LOW QUALITY PROTEIN: thyroid hormone receptor alpha-like [KO:K05547]
101642986  THRA; thyroid hormone receptor alpha [KO:K05547]
101655182  RXRA; retinoic acid receptor RXR-alpha [KO:K08524]
101641553  RXRB; retinoic acid receptor RXR-beta [KO:K08525]
101661320  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
101662560  KAT2B; histone acetyltransferase KAT2B [KO:K06062] [EC:2.3.1.48]
101655246  KAT2A; histone acetyltransferase KAT2A isoform X2 [KO:K06062] [EC:2.3.1.48]
101655793  NCOA1; nuclear receptor coactivator 1 isoform X2 [KO:K09101] [EC:2.3.1.48]
101649975  NCOA2; nuclear receptor coactivator 2 isoform X2 [KO:K11255]
101638961  NCOA3; nuclear receptor coactivator 3 isoform X2 [KO:K11256] [EC:2.3.1.48]
101641939  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
101647070  EP300; histone acetyltransferase p300 isoform X2 [KO:K04498] [EC:2.3.1.48]
101647049  MED4; mediator of RNA polymerase II transcription subunit 4 isoform X1 [KO:K15146]
101660570  MED12L; mediator of RNA polymerase II transcription subunit 12-like protein [KO:K15162]
101656659  MED12; mediator of RNA polymerase II transcription subunit 12 isoform X1 [KO:K15162]
101647763  MED13L; mediator of RNA polymerase II transcription subunit 13-like [KO:K15164]
101645739  MED13; mediator of RNA polymerase II transcription subunit 13 [KO:K15164]
101643667  MED14; mediator of RNA polymerase II transcription subunit 14 [KO:K15156]
101662891  mediator of RNA polymerase II transcription subunit 14-like [KO:K15156]
101642950  MED16; mediator of RNA polymerase II transcription subunit 16 isoform X1 [KO:K15159]
101641437  MED17; mediator of RNA polymerase II transcription subunit 17 [KO:K15133]
101641944  MED24; mediator of RNA polymerase II transcription subunit 24 isoform X1 [KO:K15167]
101656413  MED27; mediator of RNA polymerase II transcription subunit 27 [KO:K15170]
101661974  MED30; mediator of RNA polymerase II transcription subunit 30 [KO:K15143]
101637969  MED1; mediator of RNA polymerase II transcription subunit 1 [KO:K15144]
101657154  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
101642683  GATA4; transcription factor GATA-4 isoform X2 [KO:K09183]
101663022  RCAN1; calcipressin-1 [KO:K17901]
101658427  HIF1A; hypoxia-inducible factor 1-alpha [KO:K08268]
101649029  MYC; myc proto-oncogene protein isoform X3 [KO:K04377]
101661465  LOW QUALITY PROTEIN: myosin-7 [KO:K17751]
101661144  myosin-6 [KO:K17751]
101661059  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
101639123  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
101651580  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
101644023  PLN; cardiac phospholamban [KO:K05852]
101647219  WNT4; protein Wnt-4 [KO:K00408]
101656388  CTNNB1; catenin beta-1 [KO:K02105]
101652666  NOTCH1; neurogenic locus notch homolog protein 1 [KO:K02599]
101648334  NOTCH2; neurogenic locus notch homolog protein 2 [KO:K20994]
101662942  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
101647029  NOTCH4; neurogenic locus notch homolog protein 4 [KO:K20996]
101653730  BMP4; bone morphogenetic protein 4 [KO:K04662]
101651304  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101650582  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
101647679  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
101656854  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
101660344  PLCD4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 [KO:K05857] [EC:3.1.4.11]
101648979  PLCD3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 [KO:K05857] [EC:3.1.4.11]
101643603  PLCD1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 [KO:K05857] [EC:3.1.4.11]
101659910  PLCE1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 [KO:K05860] [EC:3.1.4.11]
101651012  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
101644253  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
101645146  PLCZ1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 [KO:K05861] [EC:3.1.4.11]
101638289  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101657103  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
101651846  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
101656593  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
101648541  sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
101651601  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
101659884  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
101648011  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
101650239  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
101656219  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
101658188  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
101663646  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
123520896  FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538]
101652254  SLC16A2; monocarboxylate transporter 8 [KO:K08231]
101663395  SLC16A10; monocarboxylate transporter 10 [KO:K08187]
101640115  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
101641853  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101654217  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101640675  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101655654  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101659995  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101657368  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101661509  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
101643102  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101649881  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101655315  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101657537  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101658440  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
101663717  TSC2; tuberin isoform X1 [KO:K07207]
101648247  RHEB; GTP-binding protein Rheb [KO:K07208]
101664135  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
101655785  TBC1D4; TBC1 domain family member 4 [KO:K17902]
101649569  PFKFB2; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 isoform X1 [KO:K19029] [EC:2.7.1.105 3.1.3.46]
101658729  BAD; bcl2-associated agonist of cell death [KO:K02158]
101661221  FOXO1; forkhead box protein O1 [KO:K07201]
101659735  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
101651603  RCAN2; calcipressin-2 isoform X1 [KO:K17903]
101659113  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
101660140  ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
101653492  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
101641467  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
101647792  SLCO1C1; solute carrier organic anion transporter family member 1C1 isoform X1 [KO:K08747]
101655004  DIO1; type I iodothyronine deiodinase isoform X1 [KO:K01562] [EC:1.21.99.4]
101650089  DIO2; type II iodothyronine deiodinase [KO:K17904] [EC:1.21.99.4]
101640547  DIO3; thyroxine 5-deiodinase [KO:K07754] [EC:1.21.99.3]
101659333  LOW QUALITY PROTEIN: actin, cytoplasmic 2-like [KO:K05692]
Compound
C00076  Calcium cation
C00080  H+
C00165  Diacylglycerol
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01829  Thyroxine
C02465  Triiodothyronine
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C07639  3,3',5'-Triiodo-L-thyronine
Reference
PMID:20051527
  Authors
Cheng SY, Leonard JL, Davis PJ
  Title
Molecular aspects of thyroid hormone actions.
  Journal
Endocr Rev 31:139-70 (2010)
DOI:10.1210/er.2009-0007
Reference
PMID:16214361
  Authors
Davis PJ, Davis FB, Cody V
  Title
Membrane receptors mediating thyroid hormone action.
  Journal
Trends Endocrinol Metab 16:429-35 (2005)
DOI:10.1016/j.tem.2005.09.007
Reference
PMID:18329679
  Authors
Davis PJ, Davis FB, Lin HY
  Title
Promotion by thyroid hormone of cytoplasm-to-nucleus shuttling of thyroid hormone receptors.
  Journal
Steroids 73:1013-7 (2008)
DOI:10.1016/j.steroids.2007.12.030
Reference
PMID:22484490
  Authors
Pascual A, Aranda A
  Title
Thyroid hormone receptors, cell growth and differentiation.
  Journal
Biochim Biophys Acta 1830:3908-16 (2013)
DOI:10.1016/j.bbagen.2012.03.012
Reference
PMID:17983645
  Authors
Davis PJ, Leonard JL, Davis FB
  Title
Mechanisms of nongenomic actions of thyroid hormone.
  Journal
Front Neuroendocrinol 29:211-8 (2008)
DOI:10.1016/j.yfrne.2007.09.003
Reference
PMID:19755667
  Authors
Davis PJ, Davis FB, Lin HY, Mousa SA, Zhou M, Luidens MK
  Title
Translational implications of nongenomic actions of thyroid hormone initiated at its integrin receptor.
  Journal
Am J Physiol Endocrinol Metab 297:E1238-46 (2009)
DOI:10.1152/ajpendo.00480.2009
Reference
PMID:20868274
  Authors
Davis PJ, Davis FB, Mousa SA, Luidens MK, Lin HY
  Title
Membrane receptor for thyroid hormone: physiologic and pharmacologic implications.
  Journal
Annu Rev Pharmacol Toxicol 51:99-115 (2011)
DOI:10.1146/annurev-pharmtox-010510-100512
Reference
PMID:23021374
  Authors
Lin HY, Tang HY, Davis FB, Mousa SA, Incerpi S, Luidens MK, Meng R, Davis PJ
  Title
Nongenomic regulation by thyroid hormone of plasma membrane ion and small molecule pumps.
  Journal
Discov Med 14:199-206 (2012)
Reference
PMID:21835053
  Authors
Moeller LC, Broecker-Preuss M
  Title
Transcriptional regulation by nonclassical action of thyroid hormone.
  Journal
Thyroid Res 4 Suppl 1:S6 (2011)
DOI:10.1186/1756-6614-4-S1-S6
Reference
PMID:19295177
  Authors
Bhargava M, Lei J, Ingbar DH
  Title
Nongenomic actions of L-thyroxine and 3,5,3'-triiodo-L-thyronine. Focus on "L-Thyroxine vs. 3,5,3'-triiodo-L-thyronine and cell proliferation: activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase".
  Journal
Am J Physiol Cell Physiol 296:C977-9 (2009)
DOI:10.1152/ajpcell.00116.2009
Reference
PMID:17574003
  Authors
Oetting A, Yen PM
  Title
New insights into thyroid hormone action.
  Journal
Best Pract Res Clin Endocrinol Metab 21:193-208 (2007)
DOI:10.1016/j.beem.2007.04.004
Reference
PMID:20005976
  Authors
Ojamaa K
  Title
Signaling mechanisms in thyroid hormone-induced cardiac hypertrophy.
  Journal
Vascul Pharmacol 52:113-9 (2010)
DOI:10.1016/j.vph.2009.11.008
Reference
PMID:19716314
  Authors
Aranda A, Martinez-Iglesias O, Ruiz-Llorente L, Garcia-Carpizo V, Zambrano A
  Title
Thyroid receptor: roles in cancer.
  Journal
Trends Endocrinol Metab 20:318-24 (2009)
DOI:10.1016/j.tem.2009.03.011
Reference
PMID:16951130
  Authors
Otulakowski G, O'Brodovich H
  Title
Thyroid hormone and Na+-K+-ATPase: more than simple transcription.
  Journal
Am J Physiol Lung Cell Mol Physiol 292:L4-5 (2007)
DOI:10.1152/ajplung.00332.2006
Reference
PMID:16051672
  Authors
Moeller LC, Dumitrescu AM, Refetoff S
  Title
Cytosolic action of thyroid hormone leads to induction of hypoxia-inducible factor-1alpha and glycolytic genes.
  Journal
Mol Endocrinol 19:2955-63 (2005)
DOI:10.1210/me.2004-0542
Reference
PMID:15345678
  Authors
D'Arezzo S, Incerpi S, Davis FB, Acconcia F, Marino M, Farias RN, Davis PJ
  Title
Rapid nongenomic effects of 3,5,3'-triiodo-L-thyronine on the intracellular pH of L-6 myoblasts are mediated by intracellular calcium mobilization and kinase pathways.
  Journal
Endocrinology 145:5694-703 (2004)
DOI:10.1210/en.2004-0890
Related
pathway
etf00010  Glycolysis / Gluconeogenesis
etf04010  MAPK signaling pathway
etf04020  Calcium signaling pathway
etf04066  HIF-1 signaling pathway
etf04115  p53 signaling pathway
etf04150  mTOR signaling pathway
etf04151  PI3K-Akt signaling pathway
etf04260  Cardiac muscle contraction
etf04310  Wnt signaling pathway
etf04330  Notch signaling pathway
etf04810  Regulation of actin cytoskeleton
etf04918  Thyroid hormone synthesis
KO pathway
ko04919   
LinkDB

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