ArticleThe Journal of biological chemistry2013
Phosphorylation of dopamine transporter serine 7 modulates cocaine analog binding.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 55 citations in OpenAlex.
- Hypocretin receptor 1 blockade early in abstinence prevents incubation of cocaine seeking and normalizes dopamine transmission.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Causal Mechanisms of Monoamine Transporter Phosphorylation.Advances in neurobiology · 2025Review
- Regulation of Dopamine Transporter Surface Expression.Advances in neurobiology · 2025Review
- Monoamine Transporters in Drugs of Abuse: Insights from Fast Scan Cyclic Voltammetry.Advances in neurobiology · 2025Review
- The kinase LRRK2 is required for the physiological function and expression of the glial glutamate transporter EAAT2 (SLC1A2).Journal of neurochemistry · 2025Article
- Hypocretin / Orexin Receptor 1 Knockdown in GABA or Dopamine Neurons in the Ventral Tegmental Area Differentially Impact Mesolimbic Dopamine and Motivation for Cocaine.Addiction neuroscience · 2023Article
- Dopamine transporter membrane mobility is bidirectionally regulated by phosphorylation and palmitoylation.Current research in physiology · 2023Review
- Dopamine transporter function fluctuates across sleep/wake state: potential impact for addiction.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Regulation of Glutamate, GABA and Dopamine Transporter Uptake, Surface Mobility and Expression.Frontiers in cellular neuroscience · 2021Review
- Chemogenetic Manipulation of Dopamine Neurons Dictates Cocaine Potency at Distal Dopamine Transporters.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Dopamine Evokes a Trace Amine Receptor-dependent Inward Current that is Regulated by AMP Kinase in Substantia Nigra Dopamine Neurons.Neuroscience · 2020Article
- Insulin-like growth factor 1 modulates the phosphorylation, expression, and activity of organic anion transporter 3 through protein kinase A signaling pathway.Acta pharmaceutica Sinica. B · 2020Article
- Palmitoylation by Multiple DHHC Enzymes Enhances Dopamine Transporter Function and Stability.ACS chemical neuroscience · 2019Article
- Ruboxistaurin Reduces Cocaine-Stimulated Increases in Extracellular Dopamine by Modifying Dopamine-Autoreceptor Activity.ACS chemical neuroscience · 2019Article
- Dephosphorylation of human dopamine transporter at threonine 48 by protein phosphatase PP1/2A up-regulates transport velocity.The Journal of biological chemistry · 2019Article
- Identification of the benztropine analog [Neurochemistry international · 2019Article
- Model systems for analysis of dopamine transporter function and regulation.Neurochemistry international · 2019Review
- How structural elements evolving from bacterial to human SLC6 transporters enabled new functional properties.BMC biology · 2018Article
- The role of human dopamine transporter in NeuroAIDS.Pharmacology & therapeutics · 2018Review
- Phosphorylation of the Amino Terminus of the Dopamine Transporter: Regulatory Mechanisms and Implications for Amphetamine Action.Advances in pharmacology (San Diego, Calif.) · 2018Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
As an approach to elucidating dopamine transporter (DAT) phosphorylation characteristics, we examined in vitro phosphorylation of a recombinant rat DAT N-terminal peptide (NDAT) using purified protein kinases. We found that NDAT becomes phosphorylated at single distinct sites by protein kinase A (Ser-7) and calcium-calmodulin-dependent protein kinase II (Ser-13) and at multiple sites (Ser-4, Ser-7, and Ser-13) by protein kinase C (PKC), implicating these residues as potential sites of DAT phosphorylation by these kinases. Mapping of rat striatal DAT phosphopeptides by two-dimensional thin layer chromatography revealed basal and PKC-stimulated phosphorylation of the same peptide fragments and comigration of PKC-stimulated phosphopeptide fragments with NDAT Ser-7 phosphopeptide markers. We further confirmed by site-directed mutagenesis and mass spectrometry that Ser-7 is a site for PKC-stimulated phosphorylation in heterologously expressed rat and human DATs. Mutation of Ser-7 and nearby residues strongly reduced the affinity of rat DAT for the cocaine analog (-)-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (CFT), whereas in rat striatal tissue, conditions that promote DAT phosphorylation caused increased CFT affinity. Ser-7 mutation also affected zinc modulation of CFT binding, with Ala and Asp substitutions inducing opposing effects. These results identify Ser-7 as a major site for basal and PKC-stimulated phosphorylation of native and expressed DAT and suggest that Ser-7 phosphorylation modulates transporter conformational equilibria, shifting the transporter between high and low affinity cocaine binding states.
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