Entry Name Thyroid hormone signaling pathway - Mus musculus (house mouse)
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 mmu04919 Thyroid hormone signaling pathway
Other DBs Organism Mus musculus (house mouse) [GN:
mmu ]
Gene 11931 Atp1b1; ATPase, Na+/K+ transporting, beta 1 polypeptide [KO:K01540 ]
11932 Atp1b2; ATPase, Na+/K+ transporting, beta 2 polypeptide [KO:K01540 ]
11933 Atp1b3; ATPase, Na+/K+ transporting, beta 3 polypeptide [KO:K01540 ]
11936 Fxyd2; FXYD domain-containing ion transport regulator 2 [KO:K01538 ]
11937 Atp2a1; ATPase, Ca++ transporting, cardiac muscle, fast twitch 1 [KO:K05853 ] [EC:7.2.2.10 ]
11938 Atp2a2; ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 [KO:K05853 ] [EC:7.2.2.10 ]
12015 Bad; BCL2-associated agonist of cell death [KO:K02158 ]
140781 Myh7; myosin, heavy polypeptide 7, cardiac muscle, beta [KO:K17751 ]
15251 Hif1a; hypoxia inducible factor 1, alpha subunit [KO:K08268 ]
15461 Hras; Harvey rat sarcoma virus oncogene [KO:K02833 ]
16653 Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827 ]
17888 Myh6; myosin, heavy polypeptide 6, cardiac muscle, alpha [KO:K17751 ]
17978 Ncoa2; nuclear receptor coactivator 2 [KO:K11255 ]
18706 Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
18707 Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
18708 Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
18709 Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
18710 Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
20185 Ncor1; nuclear receptor co-repressor 1 [KO:K04650 ]
20466 Sin3a; transcriptional regulator, SIN3A (yeast) [KO:K11644 ]
20502 Slc16a2; solute carrier family 16 (monocarboxylic acid transporters), member 2 [KO:K08231 ]
20525 Slc2a1; solute carrier family 2 (facilitated glucose transporter), member 1 [KO:K07299 ]
20544 Slc9a1; solute carrier family 9 (sodium/hydrogen exchanger), member 1 [KO:K05742 ]
20846 Stat1; signal transducer and activator of transcription 1 [KO:K11220 ]
22059 Trp53; transformation related protein 53 [KO:K04451 ]
22417 Wnt4; wingless-type MMTV integration site family, member 4 [KO:K00408 ]
58807 Slco1c1; solute carrier organic anion transporter family, member 1c1 [KO:K08747 ]
67821 Atp1b4; ATPase Na+/K+ transporting, beta 4 polypeptide [KO:K01540 ]
72472 Slc16a10; solute carrier family 16 (monocarboxylic acid transporters), member 10 [KO:K08187 ]
74769 Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
76199 Med13l; mediator complex subunit 13-like [KO:K15164 ]
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 mmu04810 Regulation of actin cytoskeleton
KO pathway
