Entry Name Thyroid hormone signaling pathway - Ornithorhynchus anatinus (platypus)
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 systemBRITE hierarchy
Pathway map oaa04919 Thyroid hormone signaling pathway
Ortholog table Other DBs Organism Ornithorhynchus anatinus (platypus) [GN:
oaa ]
Gene 100087266 STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220 ]
100083567 MED4; mediator of RNA polymerase II transcription subunit 4 [KO:K15146 ]
100682074 MED12L; mediator of RNA polymerase II transcription subunit 12-like protein [KO:K15162 ]
114812847 MED12; mediator of RNA polymerase II transcription subunit 12 [KO:K15162 ]
100078906 MED13; mediator of RNA polymerase II transcription subunit 13 [KO:K15164 ]
100074327 MED13L; mediator of RNA polymerase II transcription subunit 13-like [KO:K15164 ]
100082286 MED14; mediator of RNA polymerase II transcription subunit 14 [KO:K15156 ]
100079327 MED16; mediator of RNA polymerase II transcription subunit 16 isoform X1 [KO:K15159 ]
100082483 MED17; mediator of RNA polymerase II transcription subunit 17 [KO:K15133 ]
100082257 MED24; mediator of RNA polymerase II transcription subunit 24 isoform X1 [KO:K15167 ]
100074934 MED27; mediator of RNA polymerase II transcription subunit 27 [KO:K15170 ]
100078066 MED30; mediator of RNA polymerase II transcription subunit 30 [KO:K15143 ]
100092759 MED1; mediator of RNA polymerase II transcription subunit 1 [KO:K15144 ]
100086258 ATP2A3; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853 ] [EC:7.2.2.10 ]
100092718 NOTCH1; neurogenic locus notch homolog protein 1 isoform X2 [KO:K02599 ]
100081510 NOTCH2; LOW QUALITY PROTEIN: neurogenic locus notch homolog protein 2 [KO:K20994 ]
100078508 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100084272 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100083809 PLCD1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 isoform X1 [KO:K05857 ] [EC:3.1.4.11 ]
103169567 PLCE1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 [KO:K05860 ] [EC:3.1.4.11 ]
100078757 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
103167538 PLCZ1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 isoform X1 [KO:K05861 ] [EC:3.1.4.11 ]
100088125 ATP1A3; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539 ] [EC:7.2.2.13 ]
100083662 ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
100078595 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540 ]
114808215 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540 ]
100086270 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
100073788 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
100074273 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
100080187 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
100082075 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
103167126 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
100074548 SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 isoform X1 [KO:K07299 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
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 Reference Authors Davis PJ, Davis FB, Cody V
Title Membrane receptors mediating thyroid hormone action.
Journal Reference Authors Davis PJ, Davis FB, Lin HY
Title Promotion by thyroid hormone of cytoplasm-to-nucleus shuttling of thyroid hormone receptors.
Journal Reference Authors Pascual A, Aranda A
Title Thyroid hormone receptors, cell growth and differentiation.
Journal Reference Authors Davis PJ, Leonard JL, Davis FB
Title Mechanisms of nongenomic actions of thyroid hormone.
Journal 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 Reference Authors Davis PJ, Davis FB, Mousa SA, Luidens MK, Lin HY
Title Membrane receptor for thyroid hormone: physiologic and pharmacologic implications.
Journal 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 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 Reference Authors Oetting A, Yen PM
Title New insights into thyroid hormone action.
Journal Reference Authors Ojamaa K
Title Signaling mechanisms in thyroid hormone-induced cardiac hypertrophy.
Journal Reference Authors Aranda A, Martinez-Iglesias O, Ruiz-Llorente L, Garcia-Carpizo V, Zambrano A
Title Thyroid receptor: roles in cancer.
Journal Reference Authors Otulakowski G, O'Brodovich H
Title Thyroid hormone and Na+-K+-ATPase: more than simple transcription.
Journal 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 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 Related oaa04810 Regulation of actin cytoskeleton
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