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
Other DBs Orthology K00408 WNT4; wingless-type MMTV integration site family, member 4
K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K01116 PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11 ]
K01538 FXYD2, ATP1G1; sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2)
K01539 ATP1A; sodium/potassium-transporting ATPase subunit alpha [EC:7.2.2.13 ]
K01540 ATP1B, CD298; sodium/potassium-transporting ATPase subunit beta
K02158 BAD; Bcl-2-antagonist of cell death
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04377 MYC; Myc proto-oncogene protein
K04451 TP53, P53; tumor protein p53
K04503 CCND1; G1/S-specific cyclin-D1
K04650 NCOR1, N-CoR; nuclear receptor co-repressor 1
K04662 BMP4; bone morphogenetic protein 4
K05547 THRA, NR1A1; thyroid hormone receptor alpha
K05692 ACTB_G1; actin beta/gamma 1
K05742 SLC9A1, NHE1; solute carrier family 9 (sodium/hydrogen exchanger), member 1
K05857 PLCD; phosphatidylinositol phospholipase C, delta [EC:3.1.4.11 ]
K05859 PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11 ]
K05860 PLCE; phosphatidylinositol phospholipase C, epsilon [EC:3.1.4.11 ]
K06276 PDPK1; 3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1 ]
K06487 ITGAV, CD51; integrin alpha V
K06493 ITGB3, CD61; integrin beta 3
K07201 FOXO1; forkhead box protein O1
K07203 MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1 ]
K07207 TSC2; tuberous sclerosis 2
K07208 RHEB; Ras homolog enriched in brain
K07299 SLC2A1, GLUT1; MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 1
K07827 KRAS, KRAS2; GTPase KRas
K08187 SLC16A10; MFS transporter, MCT family, solute carrier family 16 (monocarboxylic acid transporters), member 10
K08231 SLC16A2; MFS transporter, MCT family, solute carrier family 16 (monocarboxylic acid transporters), member 2
K08268 HIF1A; hypoxia-inducible factor 1 alpha
K08362 THRB, NR1A2; thyroid hormone receptor beta
K08524 RXRA, NR2B1; retinoid X receptor alpha
K08525 RXRB, NR2B2; retinoid X receptor beta
K08526 RXRG, NR2B3; retinoid X receptor gamma
K08550 ESR1, NR3A1; estrogen receptor alpha
K08747 SLCO1C; solute carrier organic anion transporter family, member 1C
K09101 NCOA1, SRC1, KAT13A; nuclear receptor coactivator 1 [EC:2.3.1.48 ]
K09183 GATA4; GATA-binding protein 4
K11220 STAT1; signal transducer and activator of transcription 1
K11255 NCOA2, TIF2, KAT13C; nuclear receptor coactivator 2
K11256 NCOA3, ACTR, KAT13B; nuclear receptor coactivator 3 [EC:2.3.1.48 ]
K11644 SIN3A; paired amphipathic helix protein Sin3a
K15133 MED17; mediator of RNA polymerase II transcription subunit 17
K15143 MED30; mediator of RNA polymerase II transcription subunit 30
K15144 MED1; mediator of RNA polymerase II transcription subunit 1
K15146 MED4; mediator of RNA polymerase II transcription subunit 4
K15156 MED14, RGR1; mediator of RNA polymerase II transcription subunit 14
K15159 MED16; mediator of RNA polymerase II transcription subunit 16
K15162 MED12; mediator of RNA polymerase II transcription subunit 12
K15164 MED13; mediator of RNA polymerase II transcription subunit 13
K15167 MED24; mediator of RNA polymerase II transcription subunit 24
K15170 MED27; mediator of RNA polymerase II transcription subunit 27
K17751 MYH6_7; myosin heavy chain 6/7
K17901 RCAN1, MCIP1; calcipressin-1
K17902 TBC1D4, AS160; TBC1 domain family member 4
K17903 RCAN2, ZAKI4; calcipressin-2
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
