KEGG   PATHWAY: biu04919
Entry
biu04919                    Pathway                                
Name
Thyroid hormone signaling pathway - Bos indicus (zebu cattle)
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
biu04919  Thyroid hormone signaling pathway
biu04919

Other DBs
GO: 0002154
Organism
Bos indicus (zebu cattle) [GN:biu]
Gene
109556827  PRKACB; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
109561498  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
109565743  ITGAV; integrin alpha-V [KO:K06487]
109574140  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
109560940  GTPase HRas-like [KO:K02833]
109559581  KRAS; GTPase KRas isoform X1 [KO:K07827]
109555890  NRAS; GTPase NRas [KO:K07828]
109576053  RAF1; LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
109564697  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109561751  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
109578667  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
109570973  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109568771  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
109574238  TP53; cellular tumor antigen p53 [KO:K04451]
109573398  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
109575197  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
109572356  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
109563503  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
109562142  HDAC3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
109573677  THRA; thyroid hormone receptor alpha [KO:K05547]
109566619  RXRA; retinoic acid receptor RXR-alpha [KO:K08524]
109576548  RXRB; retinoic acid receptor RXR-beta [KO:K08525]
109577828  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
109563564  KAT2B; histone acetyltransferase KAT2B [KO:K06062] [EC:2.3.1.48]
109566334  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
109568437  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
109567523  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
109578349  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
109559852  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
109566706  MED4; mediator of RNA polymerase II transcription subunit 4 isoform X1 [KO:K15146]
109559173  mediator of RNA polymerase II transcription subunit 12-like protein isoform X1 [KO:K15162]
109555189  MED12; mediator of RNA polymerase II transcription subunit 12 [KO:K15162]
109573168  MED13; mediator of RNA polymerase II transcription subunit 13 [KO:K15164]
109571063  MED13L; mediator of RNA polymerase II transcription subunit 13-like isoform X1 [KO:K15164]
109554531  MED17; mediator of RNA polymerase II transcription subunit 17 [KO:K15133]
109574132  MED24; mediator of RNA polymerase II transcription subunit 24 [KO:K15167]
109566562  MED27; mediator of RNA polymerase II transcription subunit 27 isoform X1 [KO:K15170]
109568622  MED30; mediator of RNA polymerase II transcription subunit 30 [KO:K15143]
109573812  MED1; mediator of RNA polymerase II transcription subunit 1 isoform X1 [KO:K15144]
109554439  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
109562778  GATA4; transcription factor GATA-4 isoform X1 [KO:K09183]
109563480  RCAN1; calcipressin-1 isoform X1 [KO:K17901]
109565231  HIF1A; hypoxia-inducible factor 1-alpha [KO:K08268]
109568594  MYC; myc proto-oncogene protein [KO:K04377]
109564796  myosin-7 [KO:K17751]
109574167  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
109578141  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
109571032  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1 [KO:K05853] [EC:7.2.2.10]
109563783  PLN; cardiac phospholamban [KO:K05852]
109576138  WNT4; protein Wnt-4 [KO:K00408]
109576112  CTNNB1; catenin beta-1 [KO:K02105]
109565681  NOTCH1; LOW QUALITY PROTEIN: neurogenic locus notch homolog protein 1 [KO:K02599]
109555853  NOTCH2; neurogenic locus notch homolog protein 2 isoform X1 [KO:K20994]
109561483  NOTCH3; LOW QUALITY PROTEIN: neurogenic locus notch homolog protein 3 [KO:K20995]
109577271  NOTCH4; neurogenic locus notch homolog protein 4 [KO:K20996]
109565174  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
109554384  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
109567852  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
109567854  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
109564927  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
109576386  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 isoform X1 [KO:K05857] [EC:3.1.4.11]
109576389  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1-like [KO:K05857] [EC:3.1.4.11]
109573523  PLCD3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 [KO:K05857] [EC:3.1.4.11]
109570636  PLCD4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 isoform X1 [KO:K05857] [EC:3.1.4.11]
109553155  PLCE1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 isoform X1 [KO:K05860] [EC:3.1.4.11]
109567698  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
109572707  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
109558802  PLCZ1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 [KO:K05861] [EC:3.1.4.11]
109573366  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
109578560  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109572998  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
109573208  SLC9A1; sodium/hydrogen exchanger 1 [KO:K05742]
109578704  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
109578722  sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
109555876  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
109571737  ATP1A3; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
109555144  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
109574423  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
109570324  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
109559642  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
109569778  FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538]
109555454  SLC16A2; monocarboxylate transporter 8 [KO:K08231]
109563820  SLC16A10; monocarboxylate transporter 10 [KO:K08187]
109567428  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
109559805  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109570415  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
109557823  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
109574805  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
109561418  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109556345  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
109578066  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
109572496  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109570286  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109558399  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
109578279  TSC2; tuberin isoform X1 [KO:K07207]
109557810  RHEB; GTP-binding protein Rheb [KO:K07208]
109570401  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
109566880  TBC1D4; TBC1 domain family member 4 isoform X1 [KO:K17902]
109570439  PFKFB2; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 isoform X1 [KO:K19029] [EC:2.7.1.105 3.1.3.46]
109554386  BAD; bcl2-associated agonist of cell death [KO:K02158]
109566997  FOXO1; forkhead box protein O1 [KO:K07201]
109570433  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
109577398  RCAN2; calcipressin-2 isoform X1 [KO:K17903]
109556419  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 isoform X1 [KO:K07299]
109559166  PFKM; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
109568096  PFKP; ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
109561060  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
109559605  SLCO1C1; solute carrier organic anion transporter family member 1C1 isoform X1 [KO:K08747]
109556270  DIO1; type I iodothyronine deiodinase [KO:K01562] [EC:1.21.99.4]
109565391  DIO2; type II iodothyronine deiodinase isoform X1 [KO:K17904] [EC:1.21.99.4]
109575257  DIO3; thyroxine 5-deiodinase [KO:K07754] [EC:1.21.99.3]
109573916  ACTG1; actin, cytoplasmic 2 [KO:K05692]
109578544  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
biu00010  Glycolysis / Gluconeogenesis
biu04010  MAPK signaling pathway
biu04020  Calcium signaling pathway
biu04066  HIF-1 signaling pathway
biu04115  p53 signaling pathway
biu04150  mTOR signaling pathway
biu04151  PI3K-Akt signaling pathway
biu04260  Cardiac muscle contraction
biu04310  Wnt signaling pathway
biu04330  Notch signaling pathway
biu04810  Regulation of actin cytoskeleton
biu04918  Thyroid hormone synthesis
KO pathway
ko04919   
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