Cited by 456Neuroscience and Neuropharmacology ResearchProtein Kinase Regulation and GTPase SignalingNeurotransmitter Receptor Influence on Behavior

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Tyrosine hydroxylase phosphorylation: regulation and consequences

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Dunkley, Peter R., Bobrovskaya, Larisa, Graham, Mark E., Von Nagy‐Felsobuki, Ellak I., Dickson, Phillip W.·2004·Journal of Neurochemistry

DOI 10.1111/j.1471-4159.2004.02797.x

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Abstract

The rate‐limiting enzyme in catecholamine synthesis is tyrosine hydroxylase. It is phosphorylated at serine (Ser) residues Ser8, Ser19, Ser31 and Ser40 in vitro, in situ and in vivo. A range of protein kinases and protein phosphatases are able to phosphorylate or dephosphorylate these sites in vitro. Some of these enzymes are able to regulate tyrosine hydroxylase phosphorylation in situ and in vivo but the identity of the kinases and phosphatases is incomplete, especially for physiologically relevant stimuli. The stoichiometry of tyrosine hydroxylase phosphorylation in situ and in vivo is low. The phosphorylation of tyrosine hydroxylase at Ser40 increases the enzyme's activity in vitro, in situ and in vivo. Phosphorylation at Ser31 also increases the activity but to a much lesser extent than for Ser40 phosphorylation. The phosphorylation of tyrosine hydroxylase at Ser19 or Ser8 has no direct effect on tyrosine hydroxylase activity. Hierarchical phosphorylation of tyrosine hydroxylase occurs both in vitro and in situ, whereby the phosphorylation at Ser19 increases the rate of Ser40 phosphorylation leading to an increase in enzyme activity. Hierarchical phosphorylation depends on the state of the substrate providing a novel form of control of tyrosine hydroxylase activation.

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Specificity and mechanism of action of some commonly used protein kinase inhibitors
DAVIES, S. P., Reddy, H., Caivano, M., & Cohen, P. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3510095 · Cited by 4,366
Intricate Regulation of Tyrosine Hydroxylase Activity and Gene Expression
Kumer, S. C., & Vrana, K. E. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.67020443.x · Cited by 680
Complete coding sequence of rat tyrosine hydroxylase mRNA.
Grima, B., Lamouroux, A., Blanot, F., Biguet, N. F., & Mallet, J. J. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.2.617 · Cited by 534
Tetrahydropterin-Dependent Amino Acid Hydroxylases
Fitzpatrick, P. F. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.355 · Cited by 514
The newly synthesized selective Ca2+calmodulin dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12h cells
Sumi, M., Kiuchi, K., Ishikawa, T., Ishii, A., Hagiwara, M., Nagatsu, T., & Hidaka, H. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)92031-e · Cited by 511
B. TYROSINE HYDROXYLASE
Udenfriend, S. (1966) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)07173-x · Cited by 503
ACUTE REGULATION OF TYROSINE HYDROXYLASE BY NERVE ACTIVITY AND BY NEUROTRANSMITTERS VIA PHOSPHORYLATION
Zigmond, R. E., Schwarzschild, M. A., & Rittenhouse, A. R. (1989) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.12.030189.002215 · Cited by 495
A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics
Grima, B., Lamouroux, A., Boni, C., Julien, J., Javoy-Agid, F., & Mallet, J. J. (1987) · Nature · doi:10.1038/326707a0 · Cited by 351
Pterin-Dependent Amino Acid Hydroxylases
Kappock, T. J., & Caradonna, J. P. (1996) · Chemical Reviews · doi:10.1021/cr9402034 · Cited by 331
Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation.
JOH, T. H., Park, D. H., & Reis, D. J. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.10.4744 · Cited by 284

Show all 117 references

Research works printed but not linked: 4

10.1042/bj3510095 · DOI
Haycock J. W., 1993, Phosphorylation of tyrosine hydroxylase isoforms in human neuroblastoma cells, Mol. Biol. Cell, 41, 406a
Waymire J., 1993, Multiple site phosphorylation and activation of tyrosine hydroxylase, Adv. Prot. Phosphatases, 7, 495
Yamauchi T., 1980, Involvement of calmodulin in the Ca2+‐dependent activation of rat brainstem tyrosine 3‐monooxygenase, Biochem. Int., 1, 98

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Background
Small genetic variation affecting mRNA isoforms associated with marbling and meat color in beef cattle
Muniz, M. M. M., Fonseca, L. F. S., Silva, D. B. D. S., Magalhães, A. F. B., Ferro, J. A., Chardulo, L. A. L., Baldi, F. S., Cánovas, Á., & de Albuquerque, L. G. (2022) · Functional & Integrative Genomics · doi:10.1007/s10142-022-00844-w · Cited by 4
Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function
Parker, L. M., Damanhuri, H. A., Fletcher, S., et al. (2015) · Brain Research · doi:10.1016/j.brainres.2015.01.049 · Cited by 4
“…significantly increased in the adrenal medulla 60 min following HDZ administration, likely in order to replenish adrenal catecholamine levels (Dunkley et al., 2004), in response to the early catecholamine release shown previously to occur within 30 min of HDZ administration (Madden et al.,…”
Influential
Patterns of phosphorylated tyrosine hydroxylase vary with song production in female starlings
Ellis, J. M. S., & Riters, L. V. (2012) · Brain Research · doi:10.1016/j.brainres.2012.12.020 · Cited by 4
“Tyrosine hydroxylase (TH) is a rate-limiting enzyme in the synthesis of dopamine, and phosphorylation of TH occurs during short-term regulation of this enzyme and triggers synthesis of catecholamines (Dunkley et al., 2004; Kumer and Vrana, 1996; Lew et al., 1999).”
Background
Dopaminergic Neurotransmission
Schetz, J. A., & Sibley, D. R. (2007) · doi:10.1002/9780470101001.hcn007 · Cited by 4
Age-related decline of PKA-RIIβ level in SNc dopaminergic neurons underlies PD pathogenesisPreprint
Zhao, Y., Wang, B., Zhao, M., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.13.612981 · Cited by 4
Hypoactivity and neurochemical alterations in the basal ganglia of female Sprague-Dawley rats after repeated exposure to atrazine
Acevedo-Huergo, T., Sánchez-Yépez, J., Mendoza-Trejo, M. S., Hernández-Plata, I., Giòrdano, M., & Rodríguez, V. M. (2024) · Frontiers in Toxicology · doi:10.3389/ftox.2024.1416708 · Cited by 3
The Regulation of Catecholamine Biosynthesis by the Gas Transmitters Carbon Monoxide and Hydrogen Sulfide
Dingley, R., Hourtovenko, C., Lee, J. D., Tharmalingam, S., & Tai, T. C. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47090725 · Cited by 3
“This activation may be a result of phosphorylation of Ser31 [89], a critical serine residue [90].”
Distinctive characteristics of dopamine neuron release mechanisms: Insights into Parkinson’s Disease
Martino, E. D., Maduro, S., Luchicchi, A., Wilhelmus, M. M. M., & Orefice, N. S. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.119534 · Cited by 3
cDNA cloning and induction of tyrosine hydroxylase gene from the diamondback moth, Plutella xylostella
Hwang, S. H., Cho, S., & Park, Y. C. (2010) · Archives of Insect Biochemistry and Physiology · doi:10.1002/arch.20384 · Cited by 3
“PP2A and PP2C are believed to dephosphorylate TH at Ser40 to inactivate the protein (Dunkley et al., 2004).”
BackgroundMethod
Role of phosphodiesterases in dopamine signal transduction.
Nishi, A., Kuroiwa, M., & Shuto, T. (2010) · Folia Pharmacologica Japonica · doi:10.1254/fpj.135.8 · Cited by 3
Gender‐specific regulation of tyrosine hydroxylase in thymocyte differentiation antigen‐1 knockout mice
Carkaci‐Salli, N., Battula, S., Wang, X., Connor, J. R., & Vrana, K. E. (2012) · Journal of Neuroscience Research · doi:10.1002/jnr.23046 · Cited by 3
“DOI: 10.1002/jnr.23046 ' 2012 Wiley Periodicals, Inc. (BH4) as cosubstrates, and is the subject of extensive transcriptional and posttranslational regulation (Kumer and Vrana, 1996; Dunkley et al., 2004).”
BackgroundInfluential
Increase in tetrahydrobiopterin concentration with aging in the cerebral cortex of the senescence-accelerated mouse prone 10 strain caused by abnormal regulation of tetrahydrobiopterin biosynthesis
Miyajima, M., Minoshima, M., Tanaka, M., et al. (2013) · Biogerontology · doi:10.1007/s10522-013-9452-5 · Cited by 3
Role of the Adrenal Medulla in Hypoglycaemia-Associated Autonomic Failure—A Diabetic Perspective
Senthilkumaran, M., Koch, C., Herselman, M. F., & Bobrovskaya, L. (2024) · Metabolites · doi:10.3390/metabo14020100 · Cited by 5
“…global gene profiling in the adrenal gland, reported a significant increase in the expression of several adrenal peptides including NPY, galanin, proenkephalin, and PP2A, a common phosphatase that can dephosphorylate TH and AADC [101,141] in response to recurrent insulin-induced hypoglycaemia [37].”
BackgroundSelf-citation
Transient receptor potential ankyrin 1 channel modulates the abuse‐related mechanisms of methamphetamine through interaction with dopamine transporter
Hur, K., Lee, Y., Donio, A. L., Kim, S., Lee, B., Seo, J., Kundu, D., Kim, K., Kohut, S. J., Lee, S., et al. (2024) · British Journal of Pharmacology · doi:10.1111/bph.16370 · Cited by 3
O- GlcNAcylation regulates tyrosine hydroxylase serine 40 phosphorylation and l -DOPA levels
Rodrigues, B. D. C., Lucena, M. C., Costa, A. C. R., Oliveira, I. D. A., Thaumaturgo, M. A. S., Paes-Colli, Y., Beckman, D., Ferreira, S. T., Mello, F. G. D., Reis, R. A. D. M., et al. (2025) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00215.2024 · Cited by 3
Effects of Prenatal Stress on the Formation of the Orexinergic System of the Hypothalamus in Rats
Morina, I. Y., Петровна, С. Е., & Romanova, I. V. (2020) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-020-00942-x · Cited by 3
Enhanced Assymetrical Noradrenergic Transmission in the Olfactory Bulb of Deoxycorticosterone Acetate-Salt Hypertensive Rats
Abramoff, T., Guil, M. J., Morales, V. P., et al. (2013) · Neurochemical Research · doi:10.1007/s11064-013-1114-0 · Cited by 3
A Catecholamine Precursor Does Not Influence Exercise Performance in Warm Conditions
Cordery, P., James, L. J., Peirce, N., Maughan, R. J., & Watson, P. (2015) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000791 · Cited by 3
“Tyrosine hydroxylase is the rate-limiting enzyme in the synthesis of catecholamines and, under normal physiological conditions, is close to saturation (11).”
Background
Peripheral Lipopolysaccharide Challenge Induces Long-Term Changes in Tyrosine Hydroxylase Regulation in the Adrenal Medulla
Ong, L. K., Page, S. L., Briggs, G. D., Guan, L., Dun, M. D., Verrills, N. M., Dunkley, P. R., & Dickson, P. W. (2016) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25839 · Cited by 3
“Thirdly, we examined potential mediators of TH regulation including protein kinases (ERK1/2 for Ser31; PKA and PKC for Ser40) and protein phosphatase (PP2A for Ser31 and Ser40) activities.”
BackgroundInfluentialSelf-citation
Decreased 14‐3‐3 expression correlates with age‐related regional reductions in CNS dopamine and motor function in the pond snail, Lymnaea
Morgan, L. D., Mohammed, A., Patel, B. A., et al. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.15033 · Cited by 3
“In vitro studies have shown that phosphorylation of both serines at positions 19 and 40 can increase TH activity by 1.5- to 2-fold (Dunkley et al., 2004; Fitzpatrick, 1999).”
BackgroundInfluential
Increased Activity of Tyrosine Hydroxylase Leads to Elevated Amphetamine Response and Markers of Oxidative Stress in Transgenic MicePreprint
Vecchio, L. M., Bermejo, M. K., Dunn, A. R., Milenkovic, M., Urs, N. M., Ramsey, A. J., Miller, G. W., & Salahpour, A. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/188318 · Cited by 3
“Membranes were incubated overnight (4°C) in solutions containing rabbit anti-phosphoTH-Ser19 (1:2000; Phospho Solutions, p1580-19), rabbit anti-phosphoTH-Ser31 (1:1000; Phospho Solutions, p1580-31) or rabbit anti-phosphoTH-Ser40 (1:2000; Phospho Solutions, p1580-40).”
BackgroundInfluential
PINK1 Regulates Dopamine and Lipids at Mitochondria to Maintain Synapses and Neuronal FunctionPreprint
Bus, C., Geisler, S., Feldkaemper, M. P., Flores‐Romero, H., Schaedler, A., Zittlau, K. I., Zarani, M., Uysal, B., Casadei, N., Fallier‐Becker, P., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/814343 · Cited by 3
“After washing and fixation with 2.5% glutaraldehyde (Science Services, Munich, Germany) in cacodylate buffer (pH7.”
BackgroundInfluential
Tyrosine hydroxylase inhibits HCC progression by downregulating TGFβ/Smad signaling
Liu, G., Li, M., Zeng, Z., et al. (2024) · European journal of medical research · doi:10.1186/s40001-024-01703-z · Cited by 2
“Numerous studies have been performed to identify the kinases for the phosphorylation of S40 in TH [21], and eight different protein kinases were found [23–26].”
Background
Phosphodiesterase inhibition and Gucy2C activation enhance tyrosine hydroxylase Ser40 phosphorylation and improve 6-hydroxydopamine-induced motor deficits
Douma, E. H., Stoop, J., Lingl, M. V. R., Smidt, M. P., & van der Heide, L. P. (2024) · Cell & Bioscience · doi:10.1186/s13578-024-01312-7 · Cited by 2
“A wealth of data described that tyrosine hydroxylase is affected by the cAMP second messenger system [21, 26–31].”
BackgroundInfluential
Changes in Behavioral Characteristics and Tyrosine Hydroxylase Levels in the Nucleus Accumbens of the Brain of DAT-HET Rats during Free Alcoholization
Antonova, I., Kutcher, E. O., Филатова, Е. В., et al. (2023) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093023020242 · Cited by 2
“TH first converts the amino acid L tyro sine into 3,4 dihydroxyphenylalanine and then into dopamine [3].”
Background
Exposure of Zebrafish Embryos to Morphine and Cocaine Induces Changes in the Levels of Dopamine and of Proteins Related to the Reward Pathway
Calderón‐García, A. Á., Sánchez‐Barba, M., & González-Núñez, V. (2024) · Fishes · doi:10.3390/fishes9070268 · Cited by 2
“These molecular changes may be responsible for the physiological effects of morphine and cocaine, not only in those brain areas related to the reward pathway but also for the systemic outcomes in the entire organism.”
Background
Prolactin Mediates Distinct Time Course Regulation of Tyrosine Hydroxylase Phosphorylation and Gene Expression in Tuberoinfundibular Dopaminergic Neurons of Female Rats
Jensik, P. J., & Arbogast, L. A. (2025) · Cells · doi:10.3390/cells14090642 · Cited by 2
“Phosphorylation of Ser40 and Ser31 increases TH activity, while phosphorylation of Ser19 increases Ser40 phosphorylation [7,8].”
Immunity in Parkinson's disease – The role of innate responses
Iyengar, A. S., Dunkley, P. R., & Dickson, P. W. (2025) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2025.578716 · Cited by 4
Self-citation
Post-translacyjne i post-transkrypcyjne mechanizmy regulacji aktywności hydroksylazy tyrozynowej w ośrodkowym układzie nerwowym-wpływ wysiłku fizycznego
Przybylska, I., Kania, D., Tymosiewicz, P., Langfort, J., & Chalimoniuk, M. (2021) · Postępy Biochemii · doi:10.18388/pb.2021_388 · Cited by 2
Calcium-dependent mechanisms involved in the modulation of tyrosine hydroxylase by endothelins in the olfactory bulb of normotensive rats
Nabhen, S. L., Guil, M. J., Saffioti, N. A., et al. (2013) · Neurochemistry International · doi:10.1016/j.neuint.2013.01.018 · Cited by 2
“Given that calcium has been involved in the regulation of TH activity and expression (Kumer and Vrana, 1996; Dunkley et al., 2004) and that the physiological responses mediated by ETs can be calcium dependent or calcium independent (Tykocki and Watts, 2010), in the present study we sought to determine the relative con…”
Influential
Short-term hypoxia increases phosphorylated tyrosine hydroxylase at Ser31 and Ser40 in rat carotid body
Kato, K., & Yamamoto, Y. (2012) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2012.11.004 · Cited by 2
Crosstalk between G protein-coupled receptors (GPCRs) and tyrosine kinase receptor (TXR) in the heart after morphine withdrawal
Almela, P., García-Carmona, J. A., Laorden, E. M., Milanés, M. V., & Laorden, M. L. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00164 · Cited by 3
p53 Inactivation leads to enhancement of tyrosine hydroxylase biosynthesis in brain dopaminergic neurons
Dorofeeva, N. A., Nikitina, L. S., Glazova, M. V., Kirillova, O. D., & Chernigovskaya, E. V. (2013) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093013020060 · Cited by 2
Tyrosine hydroxylase in the brain and its regulation by glucocorticoids
Sukhareva, E. V., Kalinina, T. S., Bulygina, V. V., & Дыгало, Н. Н. (2017) · Russian Journal of Genetics Applied Research · doi:10.1134/s2079059717030145 · Cited by 2
Effects of a Novel Psychomotor Stabilizer, IRL790, on Biochemical Measures of Synaptic Markers and Neurotransmission
Bečanović, K., de Donno, M. V., Sousa, V. C., Tedroff, J., & Svenningsson, P. (2020) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.119.264754 · Cited by 2
“Phosphorylation of TH at Ser40 increases TH activity, whereas phosphorylation at Ser31 also increases TH activity but to a lesser extent (Dunkley et al., 2004).”
Background
Comparative analysis of the nigrostriatal system in Wistar rats and rats prone to seizures
Dorofeeva, N. A., Glazova, M. V., Khudik, K. A., Nikitina, L. S., Kirillova, O. D., & Chernigovskaya, E. V. (2015) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093015030088 · Cited by 2
“On the other hand, ERK1/2 kinases can activate tyrosine hydroxylase via its phosphorylation at Ser-31 [16].”
The Role of the Interaction of p53 and the MAPK Cascade in Controlling Neuronal Differentiation in the PC12 Cell Line
Zosen, D., & Glazova, M. V. (2016) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-016-0277-y · Cited by 2
In vitro brain tyrosine hydroxylase activation in catfish Heteropneustes fossilis (Bloch): seasonal changes in involvement of cAMP-dependent protein kinase A and Ca2+ -dependent protein kinase C.
Chaube, R., & Kp, J. (2008) · PubMed · Cited by 2
Role of Glucocorticoid Receptor in the Relation between Stress and Opiate Addiction
Navarro‐Zaragoza, J., Milanés, M. V., & Laorden, M. L. (2020) · IntechOpen eBooks · doi:10.5772/intechopen.90839 · Cited by 1
“It is important to highlight that previous research has shown that ERK has a main role in the phosphorylation of TH at serine 31 in the NTS [53], supporting a synergic cooperation between the brain stress system, the noradrenergic system, and this pathway.”
Background

Authors: Dunkley, P. R., Bobrovskaya, L., Graham, M. E., Von Nagy‐Felsobuki, E. I., & Dickson, P. W.
Affiliations: University of Newcastle Australia (AU)
Corresponding author: Dunkley, Peter R.
ORCID: Dunkley, Peter R.
Bobrovskaya, Larisa
Graham, Mark E.
Dickson, Phillip W.
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2004-11-18
Volume: 91
Issue: 5
Pages: 1025-1043
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1111/j.1471-4159.2004.02797.x
OpenAlex: W2114431124
Semantic Scholar: f10f568903c3e4d7cdc660f6816f0563cabf919f
Cited by: 455
References: 117
Citations by year: 2026: 6 · 2025: 12 · 2024: 13 · 2023: 16 · 2022: 8 · 2021: 23 · 2020: 19 · 2019: 26 · 2018: 20 · 2017: 23 · 2016: 19 · 2015: 29 · 2014: 24 · 2013: 32 · 2012: 28
FWCI: 1.16
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: Medical Research Council
National Health and Medical Research Council
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: tyrosine hydroxylase, serine phosphorylation, catecholamine synthesis, protein kinases, protein phosphatase, enzyme activation, phosphorylation stoichiometry
MeSH terms: Animals, Models, Biological, Phosphoprotein Phosphatases, Phosphorylation, Protein Kinases, Serine, Tyrosine 3-Monooxygenase

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Tyrosine hydroxylase phosphorylation: regulation and consequences

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