Entry Name Thyroid hormone signaling pathway
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 ko04919 Thyroid hormone signaling pathway
Ortholog table Other DBs Orthology K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K11220 signal transducer and activator of transcription 1
K08550 estrogen receptor alpha
K08362 thyroid hormone receptor beta
K04650 nuclear receptor co-repressor 1
K11644 paired amphipathic helix protein Sin3a
K05547 thyroid hormone receptor alpha
K08524 retinoid X receptor alpha
K08525 retinoid X receptor beta
K08526 retinoid X receptor gamma
K11255 nuclear receptor coactivator 2
K15146 mediator of RNA polymerase II transcription subunit 4
K15162 mediator of RNA polymerase II transcription subunit 12
K15164 mediator of RNA polymerase II transcription subunit 13
K15156 mediator of RNA polymerase II transcription subunit 14
K15159 mediator of RNA polymerase II transcription subunit 16
K15133 mediator of RNA polymerase II transcription subunit 17
K15167 mediator of RNA polymerase II transcription subunit 24
K15170 mediator of RNA polymerase II transcription subunit 27
K15143 mediator of RNA polymerase II transcription subunit 30
K15144 mediator of RNA polymerase II transcription subunit 1
K04503 G1/S-specific cyclin-D1
K08268 hypoxia-inducible factor 1 alpha
K04377 Myc proto-oncogene protein
K00408 wingless-type MMTV integration site family, member 4
K04662 bone morphogenetic protein 4
K05742 solute carrier family 9 (sodium/hydrogen exchanger), member 1
K01539 sodium/potassium-transporting ATPase subunit alpha [EC:7.2.2.13 ]
K01540 sodium/potassium-transporting ATPase subunit beta
K01538 sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2)
K08231 MFS transporter, MCT family, solute carrier family 16 (monocarboxylic acid transporters), member 2
K08187 MFS transporter, MCT family, solute carrier family 16 (monocarboxylic acid transporters), member 10
K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K07208 Ras homolog enriched in brain
K17902 TBC1 domain family member 4
K02158 Bcl-2-antagonist of cell death
K07201 forkhead box protein O1
K07299 MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 1
K08747 solute carrier organic anion transporter family, member 1C
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 ko00010 Glycolysis / Gluconeogenesis
ko04810 Regulation of actin cytoskeleton
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