The DOI matches its Crossref record; 116 of the 117 references it cites were found in a registry or an index.
Tyrosine hydroxylase phosphorylation: regulation and consequences
Open accessAbstract
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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“α-Synuclein activates stress-related protein kinases to potentiate TH phosphorylation at serine 40, suggesting the possible mechanism of pSer40-TH elevation by α-synuclein aggregation [52,124,125].”
From Degradation of Tyrosine Hydroxylase by the Ubiquitin-Proteasome System in the Pathogenesis of Parkinson’s Disease and Dopa-Responsive Dystonia (2020) · cites this paper as [52]
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Tyrosine hydroxylase and regulation of dopamine synthesis
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BackgroundInfluentialComplexity of dopamine metabolism
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“It should also be noted that Ca 2+ dependent phosphorylation of TH (Dunkley et al., 2004) is likely to play a role in the absence of exogenously added L-DOPA.”
Metadata
- 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.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2004-11-18
- Volume
- 91
- Issue
- 5
- Pages
- 1025-1043
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- 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
- 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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