Entry Name Thyroid hormone signaling pathway - Hyaena hyaena (striped hyena)
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 hhv04919 Thyroid hormone signaling pathway
Ortholog table Other DBs Organism Hyaena hyaena (striped hyena) [GN:
hhv ]
Gene 120233455 STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
120235748 SIN3A; paired amphipathic helix protein Sin3a isoform X1 [KO:K11644 ]
120220844 MED4; mediator of RNA polymerase II transcription subunit 4 [KO:K15146 ]
120237622 MED12L; mediator of RNA polymerase II transcription subunit 12-like protein [KO:K15162 ]
120246043 MED12; mediator of RNA polymerase II transcription subunit 12 [KO:K15162 ]
120229463 MED13L; mediator of RNA polymerase II transcription subunit 13-like isoform X1 [KO:K15164 ]
120241922 MED13; mediator of RNA polymerase II transcription subunit 13 [KO:K15164 ]
120248288 MED14; mediator of RNA polymerase II transcription subunit 14 isoform X1 [KO:K15156 ]
120242400 MED16; mediator of RNA polymerase II transcription subunit 16 [KO:K15159 ]
120225692 MED17; mediator of RNA polymerase II transcription subunit 17 isoform X1 [KO:K15133 ]
120229058 MED24; mediator of RNA polymerase II transcription subunit 24 isoform X1 [KO:K15167 ]
120230138 MED27; mediator of RNA polymerase II transcription subunit 27 isoform X1 [KO:K15170 ]
120228690 MED30; mediator of RNA polymerase II transcription subunit 30 isoform X1 [KO:K15143 ]
120229010 MED1; mediator of RNA polymerase II transcription subunit 1 isoform X1 [KO:K15144 ]
120221947 NOTCH1; neurogenic locus notch homolog protein 1 isoform X1 [KO:K02599 ]
120226638 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
120232448 PLCD4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 isoform X1 [KO:K05857 ] [EC:3.1.4.11 ]
120235107 PLCD1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 isoform X1 [KO:K05857 ] [EC:3.1.4.11 ]
120222292 PLCD3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 isoform X1 [KO:K05857 ] [EC:3.1.4.11 ]
120228585 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
120243007 PLCZ1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 isoform X1 [KO:K05861 ] [EC:3.1.4.11 ]
120238233 ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
120231353 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540 ]
120242657 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540 ]
120230036 FXYD2; sodium/potassium-transporting ATPase subunit gamma [KO:K01538 ]
120233608 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
120220979 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
120246696 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
120219997 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
120239233 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
120247089 phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
120236080 SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299 ]
120243015 SLCO1C1; solute carrier organic anion transporter family member 1C1 isoform X1 [KO:K08747 ]
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 hhv04810 Regulation of actin cytoskeleton
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