ArticleMolecular pharmacology2012
Tyrosine phosphorylation of the human serotonin transporter: a role in the transporter stability and function.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Regulation of hepatic organic anion transporting polypeptide 1B-type transport function by the protein kinase LYN.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Role of Phosphorylation of Serotonin and Norepinephrine Transporters in Animal Behavior: Relevance to Neuropsychiatric Disorders.International journal of molecular sciences · 2025Review
- Causal Mechanisms of Monoamine Transporter Phosphorylation.Advances in neurobiology · 2025Review
- Prenatal Opioid and Alcohol Exposures: Association with Altered Placental Serotonin Transporter Structure and/or Expression.International journal of molecular sciences · 2024Article
- Anaplastic Lymphoma Kinase signaling stabilizes SLC3A2 expression via MARCH11 to promote neuroblastoma cell growth.Cell death and differentiation · 2024Article
- Blunted Amphetamine-induced Reinforcing Behaviors and Transporter Downregulation in Knock-in Mice Carrying Alanine Mutations at Threonine-258 and Serine-259 of Norepinephrine Transporter.Journal of molecular neuroscience : MN · 2022Article
- Article
- Gestational Age Variation in Human Placental Drug Transporters.Frontiers in pharmacology · 2022Article
- Glycogen synthase kinase-3ß supports serotonin transporter function and trafficking in a phosphorylation-dependent manner.Journal of neurochemistry · 2021Article
- Histamine Receptors Regulate the Activity, Surface Expression, and Phosphorylation of Serotonin Transporters.ACS chemical neuroscience · 2020Article
- Tyrosine Phosphorylation Regulates Plasma Membrane Expression and Stability of the Human Bile Acid Transporter ASBT (Molecular pharmaceutics · 2019Article
- Fluoride related changes in behavioral outcomes may relate to increased serotonin.Physiology & behavior · 2019Article
- Post-translational modifications of transporters.Pharmacology & therapeutics · 2018Review
- The Gain-of-Function Integrin β3 Pro33 Variant Alters the Serotonin System in the Mouse Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Role of SHP2 protein tyrosine phosphatase in SERT inhibition by enteropathogenicAmerican journal of physiology. Gastrointestinal and liver physiology · 2017Article
- Modulation of serotonin transporter function by kappa-opioid receptor ligands.Neuropharmacology · 2017Article
- Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters.Pharmacological reviews · 2016Review
- Akt-mediated regulation of antidepressant-sensitive serotonin transporter function, cell-surface expression and phosphorylation.The Biochemical journal · 2015Article
- Regulated norepinephrine transporter interaction with the neurokinin-1 receptor establishes transporter subcellular localization.The Journal of biological chemistry · 2013Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The serotonin (5-HT) transporter (SERT) regulates serotoninergic neurotransmission by clearing 5-HT released into the synaptic space. Phosphorylation of SERT on serine and threonine mediates SERT regulation. Whether tyrosine phosphorylation regulates SERT is unknown. Here, we tested the hypothesis that tyrosine-phosphorylation of SERT regulates 5-HT transport. In support of this, alkali-resistant (32)P-labeled SERT was found in rat platelets, and Src-tyrosine kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo [3,4,d]pyrimidine (PP2) decreased platelet SERT function and expression. In human placental trophoblast cells expressing SERT, PP2 reduced transporter function, expression, and stability. Although siRNA silencing of Src expression decreased SERT function and expression, coexpression of Src resulted in PP2-sensitive increases in SERT function and expression. PP2 treatment markedly decreased SERT protein stability. Compared with WT-SERT, SERT tyrosine mutants Y47F and Y142F exhibited reduced 5-HT transport despite their higher total and cell surface expression levels. Moreover, Src-coexpression increased total and cell surface expression of Y47F and Y142F SERT mutants without affecting their 5-HT transport capacity. It is noteworthy that Y47F and Y142F mutants exhibited higher protein stability compared with WT-SERT. However, similar to WT-SERT, PP2 treatment decreased the stability of Y47F and Y142F mutants. Furthermore, compared with WT-SERT, Y47F and Y142F mutants exhibited lower basal tyrosine phosphorylation and no further enhancement of tyrosine phosphorylation in response to Src coexpression. These results provide the first evidence that SERT tyrosine phosphorylation supports transporter protein stability and 5HT transport.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.