KEGG   PATHWAY: rno04919
Entry
rno04919                    Pathway                                
Name
Thyroid hormone signaling pathway - Rattus norvegicus (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
rno04919  Thyroid hormone signaling pathway
rno04919

Other DBs
GO: 0002154
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
296456  Itgav; integrin alpha-V isoform 1 precursor [KO:K06487]
29302  Itgb3; integrin beta-3 precursor [KO:K06493]
293621  Hras; GTPase HRas [KO:K02833]
367858  Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833]
24525  Kras; GTPase KRas [KO:K07827]
24605  Nras; GTPase NRas [KO:K07828]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
25124  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform beta [KO:K11220]
24842  Tp53; cellular tumor antigen p53 [KO:K04451]
24890  Esr1; estrogen receptor [KO:K08550]
24831  Thrb; thyroid hormone receptor beta isoform 2 [KO:K08362]
54299  Ncor1; nuclear receptor corepressor 1 [KO:K04650]
363067  Sin3a; paired amphipathic helix protein Sin3a [KO:K11644]
297893  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
84576  Hdac1l; histone deacetylase 1-like [KO:K06067] [EC:3.5.1.98]
84577  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
84578  Hdac3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
81812  Thra; c-erbAalpha2 isoform TRalpha2 [KO:K05547]
25271  Rxra; retinoic acid receptor RXR-alpha [KO:K08524]
361801  Rxrb; retinoic acid receptor RXR-beta [KO:K08525]
83574  Rxrg; retinoic acid receptor RXR-gamma [KO:K08526]
303539  Kat2a; histone acetyltransferase KAT2A [KO:K06062] [EC:2.3.1.48]
301164  Kat2b; histone acetyltransferase KAT2B [KO:K06062] [EC:2.3.1.48]
313929  Ncoa1; nuclear receptor coactivator 1 [KO:K09101] [EC:2.3.1.48]
83724  Ncoa2; nuclear receptor coactivator 2 [KO:K11255]
84584  Ncoa3; nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
54244  Crebbp; histone lysine acetyltransferase CREBBP [KO:K04498] [EC:2.3.1.48]
170915  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
306030  Med4; mediator of RNA polymerase II transcription subunit 4 [KO:K15146]
679693  Med12; mediator of RNA polymerase II transcription subunit 12 isoform 2 [KO:K15162]
690752  Med12l; mediator of RNA polymerase II transcription subunit 12-like protein isoform X1 [KO:K15162]
303403  Med13; mediator of RNA polymerase II transcription subunit 13 [KO:K15164]
360817  Med13l; mediator of RNA polymerase II transcription subunit 13-like [KO:K15164]
317343  Med14; mediator of RNA polymerase II transcription subunit 14 [KO:K15156]
103694537  mediator of RNA polymerase II transcription subunit 14 [KO:K15156]
299607  Med16; mediator of RNA polymerase II transcription subunit 16 [KO:K15159]
300367  Med17; mediator of RNA polymerase II transcription subunit 17 [KO:K15133]
619436  Med24; mediator of RNA polymerase II transcription subunit 24 [KO:K15167]
296612  Med27; mediator of RNA polymerase II transcription subunit 27 [KO:K15170]
299905  Med30; mediator of RNA polymerase II transcription subunit 30 isoform 2 [KO:K15143]
497991  Med1; mediator of RNA polymerase II transcription subunit 1 [KO:K15144]
58919  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
54254  Gata4; transcription factor GATA-4 [KO:K09183]
266766  Rcan1; calcipressin-1 [KO:K17901]
29560  Hif1a; hypoxia-inducible factor 1-alpha [KO:K08268]
24577  Myc; myc proto-oncogene protein [KO:K04377]
29557  Myh7; myosin-7 [KO:K17751]
29556  Myh6; myosin-6 [KO:K17751]
116601  Atp2a1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
25391  Atp2a3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
29693  Atp2a2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform b [KO:K05853] [EC:7.2.2.10]
64672  Pln; cardiac phospholamban [KO:K05852]
84426  Wnt4; protein Wnt-4 precursor [KO:K00408]
84353  Ctnnb1; catenin beta-1 [KO:K02105]
25496  Notch1; neurogenic locus notch homolog protein 1 precursor [KO:K02599]
29492  Notch2; neurogenic locus notch homolog protein 2 precursor [KO:K20994]
56761  Notch3; neurogenic locus notch homolog protein 3 precursor [KO:K20995]
406162  Notch4; neurogenic locus notch homolog protein 4 precursor [KO:K20996]
25296  Bmp4; bone morphogenetic protein 4 precursor [KO:K04662]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
24655  Plcd1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 [KO:K05857] [EC:3.1.4.11]
287745  Plcd3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 [KO:K05857] [EC:3.1.4.11]
140693  Plcd4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 [KO:K05857] [EC:3.1.4.11]
114633  Plce1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 [KO:K05860] [EC:3.1.4.11]
25738  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
29337  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
497197  Plcz1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 [KO:K05861] [EC:3.1.4.11]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
24681  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
24782  Slc9a1; sodium/hydrogen exchanger 1 [KO:K05742]
24211  Atp1a1; sodium/potassium-transporting ATPase subunit alpha-1 precursor [KO:K01539] [EC:7.2.2.13]
24212  Atp1a2; sodium/potassium-transporting ATPase subunit alpha-2 precursor [KO:K01539] [EC:7.2.2.13]
24213  Atp1a3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
29132  Atp1a4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
84396  Atp1b4; protein ATP1B4 [KO:K01540]
25650  Atp1b1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
24214  Atp1b2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
25390  Atp1b3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
29639  Fxyd2; sodium/potassium-transporting ATPase subunit gamma isoform a [KO:K01538]
259248  Slc16a2; monocarboxylate transporter 8 [KO:K08231]
170566  Slc16a10; monocarboxylate transporter 10 [KO:K08187]
83805  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
134484121  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
81745  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
314856  Mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
24855  Tsc2; tuberin [KO:K07207]
26954  Rheb; GTP-binding protein Rheb [KO:K07208]
56718  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
306117  Tbc1d4; similar to TBC1 domain family member 4 [KO:K17902]
24640  Pfkfb2; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 isoform a [KO:K19029] [EC:2.7.1.105 3.1.3.46]
64639  Bad; bcl2-associated agonist of cell death [KO:K02158]
84482  Foxo1; forkhead box protein O1 [KO:K07201]
58918  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
140666  Rcan2; calcipressin-2 [KO:K17903]
24778  Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
65152  Pfkm; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
25741  Pfkl; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
60416  Pfkp; ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
84511  Slco1c1; solute carrier organic anion transporter family member 1C1 [KO:K08747]
25430  Dio1; type I iodothyronine deiodinase isoform 1 [KO:K01562] [EC:1.21.99.4]
65162  Dio2; type II iodothyronine deiodinase [KO:K17904] [EC:1.21.99.4]
29475  Dio3; thyroxine 5-deiodinase [KO:K07754] [EC:1.21.99.3]
100361457  Actg1l1; actin, gamma 1 propeptide-like [KO:K05692]
81822  Actb; actin, cytoplasmic 1 [KO:K05692]
287876  Actg1; actin, cytoplasmic 2 [KO:K05692]
120098222  POTE ankyrin domain family member F [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
rno00010  Glycolysis / Gluconeogenesis
rno04010  MAPK signaling pathway
rno04020  Calcium signaling pathway
rno04066  HIF-1 signaling pathway
rno04115  p53 signaling pathway
rno04150  mTOR signaling pathway
rno04151  PI3K-Akt signaling pathway
rno04260  Cardiac muscle contraction
rno04310  Wnt signaling pathway
rno04330  Notch signaling pathway
rno04810  Regulation of actin cytoskeleton
rno04918  Thyroid hormone synthesis
KO pathway
ko04919   
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