Entry Name Thyroid hormone signaling pathway - Ailuropoda melanoleuca (giant panda)
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 aml04919 Thyroid hormone signaling pathway
Other DBs Organism Ailuropoda melanoleuca (giant panda) [GN:
aml ]
Gene 100463775 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
100463860 NOTCH3; neurogenic locus notch homolog protein 3 isoform X1 [KO:K20995 ]
100464781 NOTCH2; neurogenic locus notch homolog protein 2 isoform X1 [KO:K20994 ]
100464926 MED13; mediator of RNA polymerase II transcription subunit 13 [KO:K15164 ]
100466831 MED13L; LOW QUALITY PROTEIN: mediator of RNA polymerase II transcription subunit 13-like [KO:K15164 ]
100467916 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
100468234 MED1; mediator of RNA polymerase II transcription subunit 1 isoform X1 [KO:K15144 ]
100468266 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540 ]
100468384 MED30; mediator of RNA polymerase II transcription subunit 30 isoform X1 [KO:K15143 ]
100468707 MED17; mediator of RNA polymerase II transcription subunit 17 [KO:K15133 ]
100468934 NOTCH1; neurogenic locus notch homolog protein 1 isoform X1 [KO:K02599 ]
100469080 ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
100469148 PLCD4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 isoform X2 [KO:K05857 ] [EC:3.1.4.11 ]
100469732 MED14; mediator of RNA polymerase II transcription subunit 14 isoform X1 [KO:K15156 ]
100471011 MED12L; mediator of RNA polymerase II transcription subunit 12-like protein isoform X1 [KO:K15162 ]
100471309 MED12; mediator of RNA polymerase II transcription subunit 12 isoform X1 [KO:K15162 ]
100474026 STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
100474779 PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858 ] [EC:3.1.4.11 ]
100475291 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
100476035 PLCD1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 [KO:K05857 ] [EC:3.1.4.11 ]
100476056 MED4; mediator of RNA polymerase II transcription subunit 4 [KO:K15146 ]
100476486 MED16; mediator of RNA polymerase II transcription subunit 16 isoform X1 [KO:K15159 ]
100476930 SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299 ]
100478369 MED24; mediator of RNA polymerase II transcription subunit 24 isoform X2 [KO:K15167 ]
100479294 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
100479580 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
100480586 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116 ] [EC:3.1.4.11 ]
100481755 PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858 ] [EC:3.1.4.11 ]
100481780 SLCO1C1; solute carrier organic anion transporter family member 1C1 [KO:K08747 ]
100481994 PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859 ] [EC:3.1.4.11 ]
100483828 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
100484596 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540 ]
105234659 MED27; mediator of RNA polymerase II transcription subunit 27 [KO:K15170 ]
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 aml04810 Regulation of actin cytoskeleton
KO pathway
