KEGG   PATHWAY: pvp04919
Entry
pvp04919                    Pathway                                
Name
Thyroid hormone signaling pathway - Pteropus vampyrus (large flying fox)
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
pvp04919  Thyroid hormone signaling pathway
pvp04919

Other DBs
GO: 0002154
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288511  RCAN2; calcipressin-2 isoform X1 [KO:K17903]
105288623  KAT2B; histone acetyltransferase KAT2B [KO:K06062] [EC:2.3.1.48]
105288781  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105289063  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105289209  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
105289247  MED13L; mediator of RNA polymerase II transcription subunit 13-like isoform X2 [KO:K15164]
105289309  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
105289326  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
105289673  ITGAV; LOW QUALITY PROTEIN: integrin alpha-V [KO:K06487]
105289767  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
105289863  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
105290106  DIO2; type II iodothyronine deiodinase isoform X1 [KO:K17904] [EC:1.21.99.4]
105290328  CTNNB1; catenin beta-1 [KO:K02105]
105290354  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
105290425  THRB; thyroid hormone receptor beta isoform X1 [KO:K08362]
105290434  WNT4; protein Wnt-4 [KO:K00408]
105290506  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
105290575  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
105291058  PLCD4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 [KO:K05857] [EC:3.1.4.11]
105291172  PLN; cardiac phospholamban [KO:K05852]
105291225  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
105291226  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
105291301  NCOR1; nuclear receptor corepressor 1 isoform X3 [KO:K04650]
105291571  GATA4; transcription factor GATA-4 [KO:K09183]
105291989  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
105292238  MED30; mediator of RNA polymerase II transcription subunit 30 isoform X3 [KO:K15143]
105292561  MYC; myc proto-oncogene protein [KO:K04377]
105293064  PLCE1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 isoform X1 [KO:K05860] [EC:3.1.4.11]
105293851  ESR1; estrogen receptor [KO:K08550]
105294059  KRAS; GTPase KRas isoform X2 [KO:K07827]
105294412  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
105294429  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
105294565  ACTB; actin, cytoplasmic 1 isoform X1 [KO:K05692]
105295104  NCOA2; nuclear receptor coactivator 2 [KO:K11255]
105295228  SLC16A10; monocarboxylate transporter 10 [KO:K08187]
105295257  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
105295334  PLCD1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 isoform X3 [KO:K05857] [EC:3.1.4.11]
105295833  [KO:K17901]
105296513  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
105296521  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
105296550  NRAS; GTPase NRas isoform X1 [KO:K07828]
105296605  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105297029  HDAC3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
105297140  [KO:K02649]
105297506  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
105297702  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
105297815  NOTCH2; neurogenic locus notch homolog protein 2 [KO:K20994]
105297846  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
105297848  BAD; bcl2-associated agonist of cell death [KO:K02158]
105297909  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
105298051  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
105298182  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
105298481  TBC1D4; TBC1 domain family member 4 isoform X1 [KO:K17902]
105298625  NOTCH1; neurogenic locus notch homolog protein 1 [KO:K02599]
105298662  MED27; mediator of RNA polymerase II transcription subunit 27 isoform X1 [KO:K15170]
105298702  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105298737  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105298901  FOXO1; forkhead box protein O1 [KO:K07201]
105298962  DIO1; type I iodothyronine deiodinase isoform X1 [KO:K01562] [EC:1.21.99.4]
105299021  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105299190  PFKP; ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
105299281  DIO3; thyroxine 5-deiodinase [KO:K07754] [EC:1.21.99.3]
105299371  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
105299444  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105299635  MED12; mediator of RNA polymerase II transcription subunit 12 [KO:K15162]
105300019  MED4; mediator of RNA polymerase II transcription subunit 4 [KO:K15146]
105300159  [KO:K04456] [EC:2.7.11.1]
105300547  [KO:K17751]
105300548  [KO:K17751]
105300627  PLCZ1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 [KO:K05861] [EC:3.1.4.11]
105300714  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
105300716  [KO:K01539] [EC:7.2.2.13]
105300975  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
105301152  ACTG1; actin, cytoplasmic 2 [KO:K05692]
105301304  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105301329  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
105301535  MED12L; mediator of RNA polymerase II transcription subunit 12-like protein isoform X1 [KO:K15162]
105301898  MED17; mediator of RNA polymerase II transcription subunit 17 [KO:K15133]
105302098  MED13; mediator of RNA polymerase II transcription subunit 13 isoform X1 [KO:K15164]
105302247  [KO:K15159]
105302941  RXRA; retinoic acid receptor RXR-alpha [KO:K08524]
105303034  PFKL; LOW QUALITY PROTEIN: ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
105303098  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
105303144  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
105303335  TSC2; LOW QUALITY PROTEIN: tuberin [KO:K07207]
105303446  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
105303526  PLCD3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 [KO:K05857] [EC:3.1.4.11]
105303777  RHEB; GTP-binding protein Rheb [KO:K07208]
105303899  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105304017  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 isoform X1 [KO:K07299]
105304250  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
105304566  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105304583  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
105305067  SLC16A2; monocarboxylate transporter 8 [KO:K08231]
105305275  NOTCH4; neurogenic locus notch homolog protein 4 isoform X3 [KO:K20996]
105305901  MED14; mediator of RNA polymerase II transcription subunit 14 isoform X1 [KO:K15156]
105305933  HRAS; GTPase HRas isoform X1 [KO:K02833]
105306301  KAT2A; histone acetyltransferase KAT2A isoform X1 [KO:K06062] [EC:2.3.1.48]
105306542  SLCO1C1; solute carrier organic anion transporter family member 1C1 [KO:K08747]
105306744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105306854  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
105307128  [KO:K04503]
105307139  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
105307215  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105307345  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
105307512  MED24; mediator of RNA polymerase II transcription subunit 24 isoform X1 [KO:K15167]
105307514  THRA; thyroid hormone receptor alpha [KO:K05547]
105307575  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105308251  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
105308359  MED1; mediator of RNA polymerase II transcription subunit 1 [KO:K15144]
105308501  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
105308691  HIF1A; hypoxia-inducible factor 1-alpha isoform X2 [KO:K08268]
105308818  [KO:K19662] [EC:2.7.11.13]
105308916  PFKFB2; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 isoform X1 [KO:K19029] [EC:2.7.1.105 3.1.3.46]
105308956  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
105308975  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
105309232  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
105309462  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
105309827  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
111743457  [KO:K17901]
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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
pvp00010  Glycolysis / Gluconeogenesis
pvp04010  MAPK signaling pathway
pvp04020  Calcium signaling pathway
pvp04066  HIF-1 signaling pathway
pvp04115  p53 signaling pathway
pvp04150  mTOR signaling pathway
pvp04151  PI3K-Akt signaling pathway
pvp04260  Cardiac muscle contraction
pvp04310  Wnt signaling pathway
pvp04330  Notch signaling pathway
pvp04810  Regulation of actin cytoskeleton
pvp04918  Thyroid hormone synthesis
KO pathway
ko04919   

DBGET integrated database retrieval system