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Gene Review

TH  -  tyrosine hydroxylase

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Disease relevance of TH

  • One of these monoclonal antibodies, TH-2D8-2, can be used for immunocytochemical localization of TH in cell bodies, dendrites, and axons in catecholaminergic neurons (e.g., cells in the substantia nigra) of rat brain and in the cell body, neurites, and growth cones of rat pheochromocytoma cells after treatment with nerve growth factor [1].
  • Almost all principal ganglion cells were TH- and DBH-immunoreactive [2].
  • From these results, it is presumed that bergenin and norbergenin may be the active components of Mallotus japonicus in inhibiting TH, and these inhibitory effects may be partially responsible for the clinical use of Mallotus japonicus in treating peptic ulcer by reducing the availability of dopa/dopamine in vivo [3].

High impact information on TH


Biological context of TH

  • This difference could result in an altered degree of regulation by posttranslational phosphorylation and also association to cell organelle membranes of bovine TH as compared with rat TH [6].
  • The carboxy terminal region has been shown to make up the catalytic site of TH and, therefore, is conserved to a greater extent in different species than the amino terminal region, which has been shown to be mainly responsible for the regulation of the catalytic activity of TH [6].
  • The predicted amino acid sequence of bovine TH is compared with that of rat TH and shows a similarity of 66% in the amino terminal (amino acids 1-157) and 91% in the carboxy terminal (amino acids 158-491) region of the TH protein molecule [6].
  • The previously obtained cDNAs coding for bovine tyrosine hydroxylase (TH) mRNA (mRNATH) were further analyzed, and the entire nucleotide sequence was determined [6].
  • The specific activity of tyrosine hydroxylase (TH) in bovine adrenal chromaffin cells can be controlled by changing cell density [7].

Anatomical context of TH


Associations of TH with chemical compounds

  • Three of the four serine residues (Ser 8, 19, and 40) that have been shown to be substrates for various protein kinases in rat TH are also present in bovine TH and are located near the amino terminal end of the molecule [6].
  • All of the absent amino acid residues of bovine TH are missing from an alanine-rich region in the N-terminal portion of the rat and human proteins (amino acids 51-68) [10].
  • Predicted amino acid sequence of bovine tyrosine hydroxylase and its similarity to tyrosine hydroxylases from other species [6].
  • Chromaffin cells initially plated at low density (2-3 X 10(4) cells/cm2), and subsequently replated at a 10-fold higher density showed a sixfold increase in specific TH activity within 48 h, resulting from enhanced synthesis (increased number of TH molecules as demonstrated by immunotitration and blockade by cycloheximide) rather than activation [7].
  • Since neither acetylcholinesterase nor lactate dehydrogenase specific activities were increased by high cell density, it can be concluded that the contact-mediated induction of TH is rather specific, and not the result of a general process of enzyme induction [7].

Regulatory relationships of TH


Other interactions of TH

  • The colocalization of DAT with tyrosine hydroxylase (TH) or dopamine beta hydroxylase (DBH) immunoreactivities was observed in nerve terminals [16].
  • To determine whether angiotensin affects synthesis of catecholamines, the activities of TH and PNMT were examined [17].
  • The presence of the phosphodiesterase inhibitor HL 725 further increased the stimulation of TH activity by PACAP, indicating that this activation was mediated via a cascade of events initiated by cAMP [18].
  • Thus, the phosphorylation of TH in bovine chromaffin cells appears to be regulated at three sites by three separate intracellular signaling pathways--Ser19 via Ca2+/calmodulin-dependent protein kinase II; Ser31 via ERK (MAP2 kinases); and Ser40 via cAMP-dependent protein kinase [19].
  • Treatment of membranes with a phosphatidylinositol-specific phospholipase C did not remove TH, ruling out the possibility of a glycosyl phosphatidyl anchor [8].

Analytical, diagnostic and therapeutic context of TH

  • Comparison of the size of bovine and rat TH mRNA and protein by northern blot and immunoblot analyses yielded differences consistent with those predicted from the nucleotide sequence data [10].
  • Site-directed mutagenesis showed that a TH mutant in which Ser-19 was substituted by Ala retained enzymatic activity at the same level as the non-mutated enzyme, but was a poor substrate for CaM kinase II and did not bind the 14-3-3 protein [20].
  • Antibodies raised against PNMT and TH were used in an indirect immunofluorescence method [21].
  • We conclude that the PAP method can be used for quantitative immunocytochemistry of brain TH providing that optimal reaction conditions are established [22].
  • The activated TH with calpain II, characterized by high-performance gel permeation chromatography, had a reduced Mr of 120,000 from the Mr of 230,000 of native enzyme [23].


  1. Isolation, characterization, and application of monoclonal antibodies to rat tyrosine hydroxylase. Kwan, S.W., Patel, N.T., Vulliet, P.R., Hall, F.L., Denney, R.M., Shen, R.S., Westlund, K.N., Abell, C.W. J. Neurosci. Res. (1989) [Pubmed]
  2. Neuropeptide Y, enkephalin and noradrenaline coexist in sympathetic neurons innervating the bovine spleen. Biochemical and immunohistochemical evidence. Fried, G., Terenius, L., Brodin, E., Efendic, S., Dockray, G., Fahrenkrug, J., Goldstein, M., Hökfelt, T. Cell Tissue Res. (1986) [Pubmed]
  3. In vitro inhibitory effects of bergenin and norbergenin on bovine adrenal tyrosine hydroxylase. Zhang, Y.H., Fang, L.H., Lee, M.K., Ku, B.S. Phytotherapy research : PTR. (2003) [Pubmed]
  4. Selective induction of tyrosine hydroxylase by cell-cell contact in bovine adrenal chromaffin cells is mimicked by plasma membranes. Saadat, S., Thoenen, H. J. Cell Biol. (1986) [Pubmed]
  5. Laminin increases both levels and activity of tyrosine hydroxylase in calf adrenal chromaffin cells. Acheson, A., Edgar, D., Timpl, R., Thoenen, H. J. Cell Biol. (1986) [Pubmed]
  6. Predicted amino acid sequence of bovine tyrosine hydroxylase and its similarity to tyrosine hydroxylases from other species. Saadat, S., Stehle, A.D., Lamouroux, A., Mallet, J., Thoenen, H. J. Neurochem. (1988) [Pubmed]
  7. Cell contact-mediated regulation of tyrosine hydroxylase synthesis in cultured bovine adrenal chromaffin cells. Acheson, A.L., Thoenen, H. J. Cell Biol. (1983) [Pubmed]
  8. Tyrosine hydroxylase in secretory granules from bovine adrenal medulla. Evidence for an integral membrane form. Kuhn, D.M., Arthur, R., Yoon, H., Sankaran, K. J. Biol. Chem. (1990) [Pubmed]
  9. Influence of cell-cell contact on levels of tyrosine hydroxylase in cultured bovine adrenal chromaffin cells. Saadat, S., Stehle, A.D., Lamouroux, A., Mallet, J., Thoenen, H. J. Biol. Chem. (1987) [Pubmed]
  10. Isolation and nucleotide sequence of a cDNA clone encoding bovine adrenal tyrosine hydroxylase: comparative analysis of tyrosine hydroxylase gene products. D'Mello, S.R., Weisberg, E.P., Stachowiak, M.K., Turzai, L.M., Gioio, A.E., Kaplan, B.B. J. Neurosci. Res. (1988) [Pubmed]
  11. Nerve growth factor-mediated enzyme induction in primary cultures of bovine adrenal chromaffin cells: specificity and level of regulation. Acheson, A.L., Naujoks, K., Thoenen, H. J. Neurosci. (1984) [Pubmed]
  12. Vasoactive intestinal polypeptide facilitates tyrosine hydroxylase induction by cholinergic agonists in bovine adrenal chromaffin cells. Olasmaa, M., Guidotti, A., Costa, E. Mol. Pharmacol. (1992) [Pubmed]
  13. Neuropeptide Y inhibits chromaffin cell nicotinic receptor-stimulated tyrosine hydroxylase activity through a receptor-linked G protein-mediated process. Zheng, J., Zhang, P., Hexum, T.D. Mol. Pharmacol. (1997) [Pubmed]
  14. Insulin-like growth factor-I enhances tyrosine hydroxylase activation in bovine chromaffin cells. Dahmer, M.K., Hart, P.M., Perlman, R.L. J. Neurochem. (1991) [Pubmed]
  15. Both short- and long-term effects of nerve growth factor on tyrosine hydroxylase in calf adrenal chromaffin cells are blocked by S-adenosylhomocysteine hydrolase inhibitors. Acheson, A., Thoenen, H. J. Neurochem. (1987) [Pubmed]
  16. Dopamine transporter immunoreactive terminals in the bovine pineal gland. Phansuwan-Pujito, P., Boontem, P., Chetsawang, B., Ebadi, M., Govitrapong, P. Neurosci. Lett. (2006) [Pubmed]
  17. Short and long term regulation of catecholamine biosynthetic enzymes by angiotensin in cultured adrenal medullary cells. Molecular mechanisms and nature of second messenger systems. Stachowiak, M.K., Jiang, H.K., Poisner, A.M., Tuominen, R.K., Hong, J.S. J. Biol. Chem. (1990) [Pubmed]
  18. Pituitary adenylate cyclase activating polypeptide (PACAP) potently enhances tyrosine hydroxylase (TH) expression in adrenal chromaffin cells. Rius, R.A., Guidotti, A., Costa, E. Life Sci. (1994) [Pubmed]
  19. Multiple signaling pathways in bovine chromaffin cells regulate tyrosine hydroxylase phosphorylation at Ser19, Ser31, and Ser40. Haycock, J.W. Neurochem. Res. (1993) [Pubmed]
  20. Stimulus-coupled interaction of tyrosine hydroxylase with 14-3-3 proteins. Itagaki, C., Isobe, T., Taoka, M., Natsume, T., Nomura, N., Horigome, T., Omata, S., Ichinose, H., Nagatsu, T., Greene, L.A., Ichimura, T. Biochemistry (1999) [Pubmed]
  21. Ontogeny of phenylethanolamine N-methyltransferase- and tyrosine hydroxylase-like immunoreactivity in presumptive adrenaline neurones of the foetal rat central nervous system. Foster, G.A., Schultzberg, M., Goldstein, M., Hökfelt, T. J. Comp. Neurol. (1985) [Pubmed]
  22. Quantitative immunocytochemistry of tyrosine hydroxylase in rat brain. I. Development of a computer assisted method using the peroxidase-antiperoxidase technique. Benno, R.H., Tucker, L.W., Joh, T.H., Reis, D.J. Brain Res. (1982) [Pubmed]
  23. Activation of tyrosine hydroxylase by Ca2+-dependent neutral protease, calpain. Togari, A., Ichikawa, S., Nagatsu, T. Biochem. Biophys. Res. Commun. (1986) [Pubmed]
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