Entry Name Thyroid hormone signaling pathway - Myotis lucifugus (little brown bat)
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 mlf04919 Thyroid hormone signaling pathway
Ortholog table Other DBs Organism Myotis lucifugus (little brown bat) [GN:
mlf ]
Gene 102424662 STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220 ]
102418332 SIN3A; paired amphipathic helix protein Sin3a isoform X1 [KO:K11644 ]
102426231 MED4; mediator of RNA polymerase II transcription subunit 4 [KO:K15146 ]
102429519 mediator of RNA polymerase II transcription subunit 12-like protein [KO:K15162 ]
102440848 MED12; mediator of RNA polymerase II transcription subunit 12 isoform X1 [KO:K15162 ]
102434510 MED13; mediator of RNA polymerase II transcription subunit 13 [KO:K15164 ]
102437309 MED13L; LOW QUALITY PROTEIN: mediator of RNA polymerase II transcription subunit 13-like [KO:K15164 ]
102435836 MED14; mediator of RNA polymerase II transcription subunit 14 [KO:K15156 ]
102426751 MED16; mediator of RNA polymerase II transcription subunit 16 isoform X1 [KO:K15159 ]
102442253 MED17; mediator of RNA polymerase II transcription subunit 17 isoform X1 [KO:K15133 ]
102428734 MED24; mediator of RNA polymerase II transcription subunit 24 [KO:K15167 ]
102420739 LOW QUALITY PROTEIN: mediator of RNA polymerase II transcription subunit 27-like [KO:K15170 ]
102428025 mediator of RNA polymerase II transcription subunit 27 [KO:K15170 ]
102440867 MED30; mediator of RNA polymerase II transcription subunit 30 [KO:K15143 ]
102436605 MED1; mediator of RNA polymerase II transcription subunit 1 [KO:K15144 ]
102438797 ATP2A3; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853 ] [EC:7.2.2.10 ]
106695521 NOTCH1; LOW QUALITY PROTEIN: neurogenic locus notch homolog protein 1 [KO:K02599 ]
102430236 NOTCH2; LOW QUALITY PROTEIN: neurogenic locus notch homolog protein 2 [KO:K20994 ]
102424223 NOTCH3; LOW QUALITY PROTEIN: neurogenic locus notch homolog protein 3 [KO:K20995 ]
102432440 PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858 ] [EC:3.1.4.11 ]
102441813 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858 ] [EC:3.1.4.11 ]
102431544 PLCD3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 isoform X1 [KO:K05857 ] [EC:3.1.4.11 ]
102421330 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
102420000 PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X2 [KO:K05859 ] [EC:3.1.4.11 ]
102432129 ATP1A1; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539 ] [EC:7.2.2.13 ]
102422636 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X3 [KO:K01540 ]
102428886 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 isoform X1 [KO:K01540 ]
102423315 ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
102422649 PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
102441064 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
102433534 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
102427890 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649 ]
102441522 LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta-like [KO:K02649 ]
102429230 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
102426106 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
102419324 LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta-like [KO:K02649 ]
102439723 TBC1D4; LOW QUALITY PROTEIN: TBC1 domain family member 4 [KO:K17902 ]
102424587 SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 isoform X1 [KO:K07299 ]
102441938 SLCO1C1; solute carrier organic anion transporter family member 1C1 isoform X1 [KO:K08747 ]
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 mlf04810 Regulation of actin cytoskeleton
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