KEGG   PATHWAY: lve04919
Entry
lve04919                    Pathway                                
Name
Thyroid hormone signaling pathway - Lipotes vexillifer (Yangtze River dolphin)
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
lve04919  Thyroid hormone signaling pathway
lve04919

Other DBs
GO: 0002154
Organism
Lipotes vexillifer (Yangtze River dolphin) [GN:lve]
Gene
103068734  NRAS; GTPase NRas [KO:K07828]
103068751  TBC1D4; LOW QUALITY PROTEIN: TBC1 domain family member 4 [KO:K17902]
103068766  ATP2A2; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
103068907  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 isoform X1 [KO:K01540]
103068908  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
103068921  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103068930  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
103069117  [KO:K11220]
103069191  ESR1; estrogen receptor [KO:K08550]
103069618  [KO:K07208]
103070161  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
103070260  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
103070274  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
103070292  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
103070370  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103070456  SLCO1C1; solute carrier organic anion transporter family member 1C1 isoform X1 [KO:K08747]
103070724  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
103070954  PFKP; 6-phosphofructokinase type C [KO:K00850] [EC:2.7.1.11]
103070997  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
103072172  MED13L; mediator of RNA polymerase II transcription subunit 13-like [KO:K15164]
103072243  MED1; mediator of RNA polymerase II transcription subunit 1 [KO:K15144]
103072342  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
103072786  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
103072897  MED4; mediator of RNA polymerase II transcription subunit 4 isoform X1 [KO:K15146]
103073028  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
103073047  PLCD1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 [KO:K05857] [EC:3.1.4.11]
103073082  THRB; thyroid hormone receptor beta isoform X1 [KO:K08362]
103073387  HIF1A; hypoxia-inducible factor 1-alpha isoform X1 [KO:K08268]
103074112  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
103074209  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
103074236  MED16; LOW QUALITY PROTEIN: mediator of RNA polymerase II transcription subunit 16 [KO:K15159]
103074614  ATP1A4; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
103074757  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
103074814  [KO:K17904] [EC:1.21.99.4]
103074894  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 isoform X1 [KO:K01539] [EC:7.2.2.13]
103074990  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
103075350  TSC2; tuberin [KO:K07207]
103075543  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103075635  PLCZ1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 [KO:K05861] [EC:3.1.4.11]
103075984  RCAN2; calcipressin-2 isoform X1 [KO:K17903]
103076043  HRAS; GTPase HRas isoform X1 [KO:K02833]
103076365  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103076397  [KO:K15164]
103076588  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
103077047  MED17; mediator of RNA polymerase II transcription subunit 17 [KO:K15133]
103077223  ACTB; actin, cytoplasmic 1 [KO:K05692]
103077464  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103077563  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
103077579  KRAS; GTPase KRas [KO:K07827]
103077665  RCAN1; calcipressin-1 [KO:K17901]
103078167  SLC16A10; monocarboxylate transporter 10 [KO:K08187]
103078301  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
103078398  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
103078639  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
103078725  PIK3R3; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103079010  MED30; mediator of RNA polymerase II transcription subunit 30 isoform X1 [KO:K15143]
103079020  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
103079154  MED24; mediator of RNA polymerase II transcription subunit 24 isoform X1 [KO:K15167]
103079287  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
103079443  NCOA3; nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
103079896  THRA; thyroid hormone receptor alpha isoform X1 [KO:K05547]
103080109  DIO1; type I iodothyronine deiodinase [KO:K01562] [EC:1.21.99.4]
103080271  RHEB; GTP-binding protein Rheb [KO:K07208]
103080387  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1-like [KO:K07299]
103080529  KAT2A; histone acetyltransferase KAT2A isoform X1 [KO:K06062] [EC:2.3.1.48]
103080679  PLCD3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 [KO:K05857] [EC:3.1.4.11]
103080930  PLCE1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 isoform X1 [KO:K05860] [EC:3.1.4.11]
103081226  PLN; cardiac phospholamban [KO:K05852]
103081400  PFKL; 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
103081431  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
103081591  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
103081712  PLCD4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 [KO:K05857] [EC:3.1.4.11]
103081765  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
103082097  HDAC3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
103082377  PFKM; 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
103082480  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
103082805  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
103083053  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
103083591  NOTCH2; neurogenic locus notch homolog protein 2-like [KO:K20994]
103083608  BAD; bcl2 antagonist of cell death [KO:K02158]
103083851  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
103083884  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
103083889  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
103083960  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103084021  MED14; mediator of RNA polymerase II transcription subunit 14 [KO:K15156]
103084463  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
103084664  PFKFB2; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 isoform X1 [KO:K19029] [EC:2.7.1.105 3.1.3.46]
103084975  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103085303  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103085364  MED12L; mediator of RNA polymerase II transcription subunit 12-like protein [KO:K15162]
103085599  KAT2B; histone acetyltransferase KAT2B [KO:K06062] [EC:2.3.1.48]
103085693  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
103086280  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
103086311  NCOA2; nuclear receptor coactivator 2 [KO:K11255]
103086383  ACTG1; actin, cytoplasmic 2 [KO:K05692]
103086653  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
103086714  MED12; mediator of RNA polymerase II transcription subunit 12 isoform X1 [KO:K15162]
103086745  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
103086905  FOXO1; forkhead box protein O1 [KO:K07201]
103087072  ITGAV; integrin alpha-V [KO:K06487]
103087387  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
103087836  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
103087933  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103088388  NOTCH4; neurogenic locus notch homolog protein 4 [KO:K20996]
103088549  DIO3; LOW QUALITY PROTEIN: deiodinase, iodothyronine, type III [KO:K07754] [EC:1.21.99.3]
103088756  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103089257  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103089387  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
103089616  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
103089875  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
103089962  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
103090453  MYH7; myosin-7 [KO:K17751]
103090549  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
103090612  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103090716  MYH6; myosin-6 [KO:K17751]
103090769  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103091196  MED27; mediator of RNA polymerase II transcription subunit 27 isoform X1 [KO:K15170]
103091353  SLC16A2; monocarboxylate transporter 8 [KO:K08231]
103091367  GATA4; transcription factor GATA-4 [KO:K09183]
103091390  NOTCH1; neurogenic locus notch homolog protein 1 [KO:K02599]
103091436  MED13; mediator of RNA polymerase II transcription subunit 13-like [KO:K15164]
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
lve00010  Glycolysis / Gluconeogenesis
lve04010  MAPK signaling pathway
lve04020  Calcium signaling pathway
lve04066  HIF-1 signaling pathway
lve04115  p53 signaling pathway
lve04150  mTOR signaling pathway
lve04151  PI3K-Akt signaling pathway
lve04260  Cardiac muscle contraction
lve04310  Wnt signaling pathway
lve04330  Notch signaling pathway
lve04810  Regulation of actin cytoskeleton
lve04918  Thyroid hormone synthesis
KO pathway
ko04919   

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