KEGG   PATHWAY: anu04919
Entry
anu04919                    Pathway                                
Name
Thyroid hormone signaling pathway - Arvicanthis niloticus (African grass rat)
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
anu04919  Thyroid hormone signaling pathway
anu04919

Other DBs
GO: 0002154
Organism
Arvicanthis niloticus (African grass rat) [GN:anu]
Gene
117723055  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
117706647  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
117702960  Itgav; integrin alpha-V isoform X1 [KO:K06487]
117710850  Itgb3; integrin beta-3 [KO:K06493]
117706664  Hras; GTPase HRas isoform X1 [KO:K02833]
117714902  Kras; GTPase KRas isoform X1 [KO:K07827]
117706966  Nras; GTPase NRas [KO:K07828]
117715476  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
117699009  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
117696143  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
117717711  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117693439  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
117705244  Stat1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
117710574  Tp53; cellular tumor antigen p53 [KO:K04451]
117700168  Esr1; estrogen receptor isoform X1 [KO:K08550]
117705036  Thrb; thyroid hormone receptor beta isoform X1 [KO:K08362]
117712009  Ncor1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
117699213  Sin3a; paired amphipathic helix protein Sin3a [KO:K11644]
117724593  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
117709000  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
117719791  Hdac3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
117710613  Thra; thyroid hormone receptor alpha [KO:K05547]
117703056  Rxra; retinoic acid receptor RXR-alpha [KO:K08524]
117724480  Rxrb; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
117716555  Rxrg; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
117722285  Kat2b; histone acetyltransferase KAT2B [KO:K06062] [EC:2.3.1.48]
117711109  Kat2a; histone acetyltransferase KAT2A isoform X1 [KO:K06062] [EC:2.3.1.48]
117717173  Ncoa1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
117698573  Ncoa2; nuclear receptor coactivator 2 [KO:K11255]
117701476  nuclear receptor coactivator 2-like [KO:K11255]
117703461  Ncoa3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
117718741  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
117710697  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
117706357  Med4; mediator of RNA polymerase II transcription subunit 4 [KO:K15146]
117707103  Med12l; mediator of RNA polymerase II transcription subunit 12-like protein [KO:K15162]
117694341  Med12; mediator of RNA polymerase II transcription subunit 12 isoform X1 [KO:K15162]
117697754  Med13l; mediator of RNA polymerase II transcription subunit 13-like isoform X1 [KO:K15164]
117710549  Med13; mediator of RNA polymerase II transcription subunit 13 [KO:K15164]
117695487  Med14; mediator of RNA polymerase II transcription subunit 14 isoform X1 [KO:K15156]
117696145  Med16; mediator of RNA polymerase II transcription subunit 16 isoform X1 [KO:K15159]
117699841  Med17; mediator of RNA polymerase II transcription subunit 17 [KO:K15133]
117710616  Med24; mediator of RNA polymerase II transcription subunit 24 isoform X1 [KO:K15167]
117703564  Med27; mediator of RNA polymerase II transcription subunit 27 [KO:K15170]
117718901  Med30; mediator of RNA polymerase II transcription subunit 30 [KO:K15143]
117710120  Med1; mediator of RNA polymerase II transcription subunit 1 isoform X1 [KO:K15144]
117711496  Ccnd1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
117705928  Gata4; transcription factor GATA-4 isoform X1 [KO:K09183]
117717971  Rcan1; calcipressin-1 isoform X1 [KO:K17901]
117697105  Hif1a; hypoxia-inducible factor 1-alpha isoform X1 [KO:K08268]
117719150  Myc; myc proto-oncogene protein [KO:K04377]
117695826  myc proto-oncogene protein-like [KO:K04377]
117695848  myc proto-oncogene protein-like [KO:K04377]
117696009  myc proto-oncogene protein-like [KO:K04377]
117705073  myosin-6 [KO:K17751]
117705089  Myh7; myosin-7 [KO:K17751]
117697839  Atp2a2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
117705440  Atp2a1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
117710680  Atp2a3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
117724780  Pln; cardiac phospholamban [KO:K05852]
117708522  Wnt4; protein Wnt-4 [KO:K00408]
117693212  Ctnnb1; catenin beta-1 [KO:K02105]
117710516  Notch1; neurogenic locus notch homolog protein 1 [KO:K02599]
117706733  Notch2; neurogenic locus notch homolog protein 2 [KO:K20994]
117696497  Notch3; neurogenic locus notch homolog protein 3 [KO:K20995]
117724864  Notch4; neurogenic locus notch homolog protein 4 [KO:K20996]
117706351  Bmp4; bone morphogenetic protein 4 [KO:K04662]
117712005  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
117703017  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
117703351  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
117703529  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
117705062  Plcd4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 [KO:K05857] [EC:3.1.4.11]
117693356  Plcd1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 isoform X1 [KO:K05857] [EC:3.1.4.11]
117710098  Plcd3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 isoform X1 [KO:K05857] [EC:3.1.4.11]
117704993  Plce1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 isoform X1 [KO:K05860] [EC:3.1.4.11]
117703352  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
117723064  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
117715353  Plcz1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 isoform X1 [KO:K05861] [EC:3.1.4.11]
117709948  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
117717067  Prkcb; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
117701003  Prkcg; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
117708502  Slc9a1; sodium/hydrogen exchanger 1 [KO:K05742]
117707426  Atp1a3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
117707671  Atp1a1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
117721387  sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
117721554  sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
117716086  Atp1b1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
117693784  Atp1b3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
117694611  Atp1b4; protein ATP1B4 isoform X1 [KO:K01540]
117710658  Atp1b2; sodium/potassium-transporting ATPase subunit beta-2 isoform X1 [KO:K01540]
117699293  Fxyd2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538]
117694840  Slc16a2; monocarboxylate transporter 8 [KO:K08231]
117724964  Slc16a10; monocarboxylate transporter 10 [KO:K08187]
117703400  Src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
117706649  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
117693421  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
117708986  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
117721973  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
117723761  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
117708961  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
117710000  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
117697536  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117706636  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117721481  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117718295  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
117696339  Mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
117710404  Tsc2; tuberin isoform X1 [KO:K07207]
117694570  GTP-binding protein Rheb-like [KO:K07208]
117694603  GTP-binding protein Rheb-like [KO:K07208]
117720863  Rheb; GTP-binding protein Rheb [KO:K07208]
117709409  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
117706107  Tbc1d4; TBC1 domain family member 4 [KO:K17902]
117716074  Pfkfb2; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 isoform X1 [KO:K19029] [EC:2.7.1.105 3.1.3.46]
117706557  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
117706979  Foxo1; forkhead box protein O1 [KO:K07201]
117708916  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
117722465  Rcan2; calcipressin-2 isoform X1 [KO:K17903]
117708410  Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
117724408  Pfkl; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
117719354  Pfkm; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
117713608  Pfkp; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
117715110  Slco1c1; solute carrier organic anion transporter family member 1C1 [KO:K08747]
117709149  Dio1; type I iodothyronine deiodinase [KO:K01562] [EC:1.21.99.4]
117697413  Dio2; LOW QUALITY PROTEIN: type II iodothyronine deiodinase [KO:K17904] [EC:1.21.99.4]
117697357  Dio3; thyroxine 5-deiodinase [KO:K07754] [EC:1.21.99.3]
117697924  Actb; actin, cytoplasmic 1 [KO:K05692]
117710865  Actg1; actin, cytoplasmic 2 [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
  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
anu00010  Glycolysis / Gluconeogenesis
anu04010  MAPK signaling pathway
anu04020  Calcium signaling pathway
anu04066  HIF-1 signaling pathway
anu04115  p53 signaling pathway
anu04150  mTOR signaling pathway
anu04151  PI3K-Akt signaling pathway
anu04260  Cardiac muscle contraction
anu04310  Wnt signaling pathway
anu04330  Notch signaling pathway
anu04810  Regulation of actin cytoskeleton
anu04918  Thyroid hormone synthesis
KO pathway
ko04919   
LinkDB

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