Entry Name Thyroid hormone signaling pathway - Rattus norvegicus (rat)
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 rno04919 Thyroid hormone signaling pathway
Other DBs Organism Rattus norvegicus (rat) [GN:
rno ]
Gene 114633 Plce1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 [KO:K05860 ] [EC:3.1.4.11 ]
140693 Plcd4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 [KO:K05857 ] [EC:3.1.4.11 ]
170911 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
24211 Atp1a1; sodium/potassium-transporting ATPase subunit alpha-1 precursor [KO:K01539 ] [EC:7.2.2.13 ]
24212 Atp1a2; sodium/potassium-transporting ATPase subunit alpha-2 precursor [KO:K01539 ] [EC:7.2.2.13 ]
24214 Atp1b2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540 ]
24654 Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858 ] [EC:3.1.4.11 ]
24655 Plcd1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 [KO:K05857 ] [EC:3.1.4.11 ]
24778 Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299 ]
24831 Thrb; thyroid hormone receptor beta isoform 2 [KO:K08362 ]
25031 Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858 ] [EC:3.1.4.11 ]
25124 Stat1; signal transducer and activator of transcription 1-alpha/beta isoform beta [KO:K11220 ]
25271 Rxra; retinoic acid receptor RXR-alpha [KO:K08524 ]
25296 Bmp4; bone morphogenetic protein 4 precursor [KO:K04662 ]
25390 Atp1b3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540 ]
25496 Notch1; neurogenic locus notch homolog protein 1 precursor [KO:K02599 ]
25513 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
25650 Atp1b1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
25738 Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116 ] [EC:3.1.4.11 ]
287745 Plcd3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 [KO:K05857 ] [EC:3.1.4.11 ]
29322 Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858 ] [EC:3.1.4.11 ]
29337 Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859 ] [EC:3.1.4.11 ]
29492 Notch2; neurogenic locus notch homolog protein 2 precursor [KO:K20994 ]
29560 Hif1a; hypoxia-inducible factor 1-alpha [KO:K08268 ]
29639 Fxyd2; sodium/potassium-transporting ATPase subunit gamma isoform a [KO:K01538 ]
296456 Itgav; integrin alpha-V isoform 1 precursor [KO:K06487 ]
296612 Med27; mediator of RNA polymerase II transcription subunit 27 [KO:K15170 ]
29693 Atp2a2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform b [KO:K05853 ] [EC:7.2.2.10 ]
29741 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
299607 Med16; mediator of RNA polymerase II transcription subunit 16 [KO:K15159 ]
299905 Med30; mediator of RNA polymerase II transcription subunit 30 isoform 2 [KO:K15143 ]
300367 Med17; mediator of RNA polymerase II transcription subunit 17 [KO:K15133 ]
303403 Med13; mediator of RNA polymerase II transcription subunit 13 [KO:K15164 ]
306030 Med4; mediator of RNA polymerase II transcription subunit 4 [KO:K15146 ]
306117 Tbc1d4; similar to TBC1 domain family member 4 [KO:K17902 ]
317343 Med14; mediator of RNA polymerase II transcription subunit 14 [KO:K15156 ]
360817 Med13l; mediator of RNA polymerase II transcription subunit 13-like [KO:K15164 ]
363067 Sin3a; paired amphipathic helix protein Sin3a [KO:K11644 ]
366508 Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
367858 Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833 ]
406162 Notch4; neurogenic locus notch homolog protein 4 precursor [KO:K20996 ]
497197 Plcz1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 [KO:K05861 ] [EC:3.1.4.11 ]
497991 Med1; mediator of RNA polymerase II transcription subunit 1 [KO:K15144 ]
54299 Ncor1; nuclear receptor corepressor 1 [KO:K04650 ]
56761 Notch3; neurogenic locus notch homolog protein 3 precursor [KO:K20995 ]
58960 Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369 ] [EC:2.7.12.2 ]
60664 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
619436 Med24; mediator of RNA polymerase II transcription subunit 24 [KO:K15167 ]
64639 Bad; bcl2-associated agonist of cell death [KO:K02158 ]
679693 Med12; mediator of RNA polymerase II transcription subunit 12 isoform 2 [KO:K15162 ]
690752 Med12l; mediator of RNA polymerase II transcription subunit 12-like protein isoform X1 [KO:K15162 ]
83574 Rxrg; retinoic acid receptor RXR-gamma [KO:K08526 ]
83724 Ncoa2; nuclear receptor coactivator 2 [KO:K11255 ]
84511 Slco1c1; solute carrier organic anion transporter family member 1C1 [KO:K08747 ]
85240 Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858 ] [EC:3.1.4.11 ]
85243 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
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 rno04810 Regulation of actin cytoskeleton
KO pathway
