KEGG   PATHWAY: mcal04919
Entry
mcal04919                   Pathway                                
Name
Thyroid hormone signaling pathway - Mus caroli (Ryukyu mouse)
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
mcal04919  Thyroid hormone signaling pathway
mcal04919

Other DBs
GO: 0002154
Organism
Mus caroli (Ryukyu mouse) [GN:mcal]
Gene
110290795  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
110300173  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
110311058  Itgav; integrin alpha-V isoform X1 [KO:K06487]
110305072  Itgb3; integrin beta-3 [KO:K06493]
110297313  Hras; GTPase HRas isoform X2 [KO:K02833]
110296194  Kras; GTPase KRas isoform X1 [KO:K07827]
110290873  Nras; GTPase NRas [KO:K07828]
110296919  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
110301502  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110303196  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110297836  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110311382  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
110304843  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
110305297  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
110303039  Esr1; estrogen receptor isoform X1 [KO:K08550]
110308859  Thrb; thyroid hormone receptor beta isoform X3 [KO:K08362]
110305303  Ncor1; nuclear receptor corepressor 1 isoform X8 [KO:K04650]
110301308  Sin3a; paired amphipathic helix protein Sin3a isoform X1 [KO:K11644]
110292292  Hdac1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
110302836  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
110285017  Hdac3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
110305117  Thra; thyroid hormone receptor alpha [KO:K05547]
110308122  Rxra; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
110312146  Rxrb; retinoic acid receptor RXR-beta isoform X3 [KO:K08525]
110290588  Rxrg; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
110304328  Kat2a; histone acetyltransferase KAT2A isoform X1 [KO:K06062] [EC:2.3.1.48]
110312276  Kat2b; histone acetyltransferase KAT2B [KO:K06062] [EC:2.3.1.48]
110306510  Ncoa1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
110300251  Ncoa2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
110311955  Ncoa3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
110310313  Ep300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
110311224  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
110309247  Med4; mediator of RNA polymerase II transcription subunit 4 [KO:K15146]
110286467  Med12; mediator of RNA polymerase II transcription subunit 12 isoform X1 [KO:K15162]
110290740  Med12l; mediator of RNA polymerase II transcription subunit 12-like protein [KO:K15162]
110294052  Med13l; mediator of RNA polymerase II transcription subunit 13-like isoform X1 [KO:K15164]
110304840  Med13; mediator of RNA polymerase II transcription subunit 13 [KO:K15164]
110286551  Med14; mediator of RNA polymerase II transcription subunit 14 isoform X1 [KO:K15156]
110303090  Med16; mediator of RNA polymerase II transcription subunit 16 isoform X1 [KO:K15159]
110301301  Med17; mediator of RNA polymerase II transcription subunit 17 isoform X1 [KO:K15133]
110305049  Med24; mediator of RNA polymerase II transcription subunit 24 isoform X2 [KO:K15167]
110284140  Med27; mediator of RNA polymerase II transcription subunit 27 isoform X1 [KO:K15170]
110310829  Med30; mediator of RNA polymerase II transcription subunit 30 [KO:K15143]
110304197  Med1; mediator of RNA polymerase II transcription subunit 1 isoform X1 [KO:K15144]
110298189  Ccnd1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
110309538  Gata4; transcription factor GATA-4 [KO:K09183]
110311695  Rcan1; calcipressin-1 isoform X1 [KO:K17901]
110306746  Hif1a; hypoxia-inducible factor 1-alpha isoform X5 [KO:K08268]
110310583  Myc; myc proto-oncogene protein [KO:K04377]
110309088  Myh7; myosin-7 [KO:K17751]
110309092  Myh6; myosin-6 isoform X2 [KO:K17751]
110295033  Atp2a2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
110304358  Atp2a3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X2 [KO:K05853] [EC:7.2.2.10]
110299270  Atp2a1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
110303164  Pln; cardiac phospholamban [KO:K05852]
110293218  Wnt4; protein Wnt-4 isoform X1 [KO:K00408]
110301052  Ctnnb1; catenin beta-1 [KO:K02105]
110308685  Notch1; neurogenic locus notch homolog protein 1 [KO:K02599]
110290735  Notch2; neurogenic locus notch homolog protein 2 isoform X1 [KO:K20994]
110312607  Notch3; neurogenic locus notch homolog protein 3 [KO:K20995]
110312347  Notch4; neurogenic locus notch homolog protein 4 isoform X1 [KO:K20996]
110309274  Bmp4; bone morphogenetic protein 4 [KO:K04662]
110285320  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
110290514  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
110286326  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
110308867  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
110305200  Plcd3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 isoform X1 [KO:K05857] [EC:3.1.4.11]
110301135  Plcd1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 isoform X2 [KO:K05857] [EC:3.1.4.11]
110293847  Plcd4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 isoform X1 [KO:K05857] [EC:3.1.4.11]
110285551  Plce1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 isoform X5 [KO:K05860] [EC:3.1.4.11]
110290454  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
110300336  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
110296889  Plcz1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 isoform X1 [KO:K05861] [EC:3.1.4.11]
110304357  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
110297826  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
110297763  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
110292287  Slc9a1; sodium/hydrogen exchanger 1 isoform X1 [KO:K05742]
110291780  sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
110290752  Atp1a1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
110297290  Atp1a3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
110296540  sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
110290643  Atp1b1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
110287115  Atp1b4; protein ATP1B4 [KO:K01540]
110301197  Atp1b3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
110304973  Atp1b2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
110302161  Fxyd2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538]
110286585  Slc16a2; monocarboxylate transporter 8 [KO:K08231]
110303322  Slc16a10; monocarboxylate transporter 10 [KO:K08187]
110310031  Src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
110290798  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110292183  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110301355  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
110308009  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110299855  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
110292624  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
110312395  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
110297609  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110294471  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110307022  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110311365  Gsk3b; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
110303712  Mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
110284338  Tsc2; tuberin isoform X1 [KO:K07207]
110294321  Rheb; GTP-binding protein Rheb [KO:K07208]
110292680  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
110309142  Tbc1d4; TBC1 domain family member 4 isoform X1 [KO:K17902]
110296782  Pfkfb2; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 isoform X1 [KO:K19029] [EC:2.7.1.105 3.1.3.46]
110285481  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
110291168  Foxo1; forkhead box protein O1 [KO:K07201]
110293440  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
110312493  Rcan2; calcipressin-2 isoform X1 [KO:K17903]
110292203  Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
110307877  Pfkp; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
110302996  Pfkl; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
110310722  Pfkm; ATP-dependent 6-phosphofructokinase, muscle type isoform X2 [KO:K00850] [EC:2.7.1.11]
110296659  Slco1c1; solute carrier organic anion transporter family member 1C1 isoform X1 [KO:K08747]
110293582  Dio1; type I iodothyronine deiodinase isoform X1 [KO:K01562] [EC:1.21.99.4]
110307003  Dio2; LOW QUALITY PROTEIN: type II iodothyronine deiodinase [KO:K17904] [EC:1.21.99.4]
110307126  Dio3; thyroxine 5-deiodinase [KO:K07754] [EC:1.21.99.3]
110304283  Actg1; actin, cytoplasmic 2 [KO:K05692]
110295381  Actb; actin, cytoplasmic 1 [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
mcal00010  Glycolysis / Gluconeogenesis
mcal04010  MAPK signaling pathway
mcal04020  Calcium signaling pathway
mcal04066  HIF-1 signaling pathway
mcal04115  p53 signaling pathway
mcal04150  mTOR signaling pathway
mcal04151  PI3K-Akt signaling pathway
mcal04260  Cardiac muscle contraction
mcal04310  Wnt signaling pathway
mcal04330  Notch signaling pathway
mcal04810  Regulation of actin cytoskeleton
mcal04918  Thyroid hormone synthesis
KO pathway
ko04919   
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