KEGG   PATHWAY: ko04919
ko04919                     Pathway                                

Thyroid hormone signaling pathway
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.
Organismal Systems; Endocrine system
Pathway map
ko04919  Thyroid hormone signaling pathway

H00249  Thyroid hormone resistance syndrome
H00250  Congenital nongoitrous hypothyroidism (CHNG)
H00889  Lujan-Fryns syndrome
Other DBs
GO: 0002154
K04345  protein kinase A [EC:]
K06487  integrin alpha V
K06493  integrin beta 3
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:]
K04368  mitogen-activated protein kinase kinase 1 [EC:]
K04369  mitogen-activated protein kinase kinase 2 [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K11220  signal transducer and activator of transcription 1
K04451  tumor protein p53
K08550  estrogen receptor alpha
K08362  thyroid hormone receptor beta
K04650  nuclear receptor co-repressor 1
K11644  paired amphipathic helix protein Sin3a
K06067  histone deacetylase 1/2 [EC:]
K11404  histone deacetylase 3 [EC:]
K05547  thyroid hormone receptor alpha
K08524  retinoid X receptor alpha
K08525  retinoid X receptor beta
K08526  retinoid X receptor gamma
K06062  histone acetyltransferase [EC:]
K09101  nuclear receptor coactivator 1 [EC:]
K11255  nuclear receptor coactivator 2
K11256  nuclear receptor coactivator 3 [EC:]
K04498  E1A/CREB-binding protein [EC:]
K15146  mediator of RNA polymerase II transcription subunit 4
K15162  mediator of RNA polymerase II transcription subunit 12
K15164  mediator of RNA polymerase II transcription subunit 13
K15156  mediator of RNA polymerase II transcription subunit 14
K15159  mediator of RNA polymerase II transcription subunit 16
K15133  mediator of RNA polymerase II transcription subunit 17
K15167  mediator of RNA polymerase II transcription subunit 24
K15170  mediator of RNA polymerase II transcription subunit 27
K15143  mediator of RNA polymerase II transcription subunit 30
K15144  mediator of RNA polymerase II transcription subunit 1
K04503  G1/S-specific cyclin-D1
K09183  GATA-binding protein 4
K17901  calcipressin-1
K08268  hypoxia-inducible factor 1 alpha
K04377  Myc proto-oncogene protein
K17751  myosin heavy chain 6/7
K05853  P-type Ca2+ transporter type 2A [EC:]
K05852  phospholamban
K00408  wingless-type MMTV integration site family, member 4
K02105  catenin beta 1
K02599  Notch 1
K20994  Notch 2
K20995  Notch 3
K20996  Notch 4
K04662  bone morphogenetic protein 4
K05858  phosphatidylinositol phospholipase C, beta [EC:]
K05857  phosphatidylinositol phospholipase C, delta [EC:]
K05860  phosphatidylinositol phospholipase C, epsilon [EC:]
K01116  phosphatidylinositol phospholipase C, gamma-1 [EC:]
K05859  phosphatidylinositol phospholipase C, gamma-2 [EC:]
K05861  phosphatidylinositol phospholipase C, zeta [EC:]
K01114  phospholipase C [EC:]
K02677  classical protein kinase C alpha type [EC:]
K19662  classical protein kinase C beta type [EC:]
K19663  classical protein kinase C gamma type [EC:]
K05742  solute carrier family 9 (sodium/hydrogen exchanger), member 1
K01539  sodium/potassium-transporting ATPase subunit alpha [EC:]
K01540  sodium/potassium-transporting ATPase subunit beta
K01538  sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2)
K08231  MFS transporter, MCT family, solute carrier family 16 (monocarboxylic acid transporters), member 2
K08187  MFS transporter, MCT family, solute carrier family 16 (monocarboxylic acid transporters), member 10
K05704  tyrosine-protein kinase Src [EC:]
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K06276  3-phosphoinositide dependent protein kinase-1 [EC:]
K04456  RAC serine/threonine-protein kinase [EC:]
K03083  glycogen synthase kinase 3 beta [EC:]
K06643  E3 ubiquitin-protein ligase Mdm2 [EC:]
K07207  tuberous sclerosis 2
K07208  Ras homolog enriched in brain
K07203  serine/threonine-protein kinase mTOR [EC:]
K17902  TBC1 domain family member 4
K19029  6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 2 [EC:]
K02158  Bcl-2-antagonist of cell death
K07201  forkhead box protein O1
K04399  caspase 9 [EC:]
K17903  calcipressin-2
K07299  MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 1
K00850  6-phosphofructokinase 1 [EC:]
K08747  solute carrier organic anion transporter family, member 1C
K01562  type I thyroxine 5'-deiodinase [EC:]
K17904  type II thyroxine 5'-deiodinase [EC:]
K07754  thyroxine 5-deiodinase [EC:]
K05692  actin beta/gamma 1
C00076  Calcium cation
C00080  H+
C00165  Diacylglycerol
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01829  Thyroxine
C02465  Triiodothyronine
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C07639  3,3',5'-Triiodo-L-thyronine
Cheng SY, Leonard JL, Davis PJ
Molecular aspects of thyroid hormone actions.
Endocr Rev 31:139-70 (2010)
Davis PJ, Davis FB, Cody V
Membrane receptors mediating thyroid hormone action.
Trends Endocrinol Metab 16:429-35 (2005)
Davis PJ, Davis FB, Lin HY
Promotion by thyroid hormone of cytoplasm-to-nucleus shuttling of thyroid hormone receptors.
Steroids 73:1013-7 (2008)
Pascual A, Aranda A
Thyroid hormone receptors, cell growth and differentiation.
Biochim Biophys Acta 1830:3908-16 (2013)
Davis PJ, Leonard JL, Davis FB
Mechanisms of nongenomic actions of thyroid hormone.
Front Neuroendocrinol 29:211-8 (2008)
Davis PJ, Davis FB, Lin HY, Mousa SA, Zhou M, Luidens MK
Translational implications of nongenomic actions of thyroid hormone initiated at its integrin receptor.
Am J Physiol Endocrinol Metab 297:E1238-46 (2009)
Davis PJ, Davis FB, Mousa SA, Luidens MK, Lin HY
Membrane receptor for thyroid hormone: physiologic and pharmacologic implications.
Annu Rev Pharmacol Toxicol 51:99-115 (2011)
Lin HY, Tang HY, Davis FB, Mousa SA, Incerpi S, Luidens MK, Meng R, Davis PJ
Nongenomic regulation by thyroid hormone of plasma membrane ion and small molecule pumps.
Discov Med 14:199-206 (2012)
Moeller LC, Broecker-Preuss M
Transcriptional regulation by nonclassical action of thyroid hormone.
Thyroid Res 4 Suppl 1:S6 (2011)
Bhargava M, Lei J, Ingbar DH
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".
Am J Physiol Cell Physiol 296:C977-9 (2009)
Oetting A, Yen PM
New insights into thyroid hormone action.
Best Pract Res Clin Endocrinol Metab 21:193-208 (2007)
Ojamaa K
Signaling mechanisms in thyroid hormone-induced cardiac hypertrophy.
Vascul Pharmacol 52:113-9 (2010)
Aranda A, Martinez-Iglesias O, Ruiz-Llorente L, Garcia-Carpizo V, Zambrano A
Thyroid receptor: roles in cancer.
Trends Endocrinol Metab 20:318-24 (2009)
Otulakowski G, O'Brodovich H
Thyroid hormone and Na+-K+-ATPase: more than simple transcription.
Am J Physiol Lung Cell Mol Physiol 292:L4-5 (2007)
Moeller LC, Dumitrescu AM, Refetoff S
Cytosolic action of thyroid hormone leads to induction of hypoxia-inducible factor-1alpha and glycolytic genes.
Mol Endocrinol 19:2955-63 (2005)
D'Arezzo S, Incerpi S, Davis FB, Acconcia F, Marino M, Farias RN, Davis PJ
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.
Endocrinology 145:5694-703 (2004)
ko00010  Glycolysis / Gluconeogenesis
ko04010  MAPK signaling pathway
ko04020  Calcium signaling pathway
ko04066  HIF-1 signaling pathway
ko04115  p53 signaling pathway
ko04150  mTOR signaling pathway
ko04151  PI3K-Akt signaling pathway
ko04260  Cardiac muscle contraction
ko04310  Wnt signaling pathway
ko04330  Notch signaling pathway
ko04510  Focal adhesion
ko04810  Regulation of actin cytoskeleton
ko04918  Thyroid hormone synthesis

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