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http://dx.doi.org/10.5352/JLS.2010.20.10.1451

Protein Kinase (PKC)-ε Interacts with the Serotonin Transporter (SERT) C-Terminal Region  

Moon, Il-Soo (Department of Anatomy, College of Medicine, Dongguk University)
Seog, Dae-Hyun (Department of Biochemistry, College of Medicine, Inje University)
Publication Information
Journal of Life Science / v.20, no.10, 2010 , pp. 1451-1457 More about this Journal
Abstract
Serotonin (5-hydroxytryptamine, 5-HT) is an important mediator of cell-cell signaling in neuronal systems. The serotonin transporter (SERT) on the plasma membrane controls the extracellular 5-HT level by reuptake of released 5-HT from the synaptic cleft, but the underlying regulation mechanism is unclear. Here, we used the yeast two-hybrid system to identify the specific binding protein(s) that interacts with the carboxyl (C)-terminal region of SERT and found a specific interaction with protein kinase C-$\varepsilon$ (PKC-$\varepsilon$), a PKC isotype that is characterized as a calcium-independent and phorbol ester/diacylglycerol-sensitive serine/threonine kinase. PKC-$\varepsilon$ bound to the tail region of SERT but not to other members of the $Na^+/Cl^-$ dependent SLC6 gene family in the yeast two-hybrid assay. The C-terminal region of PKC-$\varepsilon$ is essential for interaction with SERT. In addition, these proteins showed specific interactions in the glutathione S-transferase (GST) pull-down assay. PKC-$\varepsilon$ phosphorylated the peptide of the SERT amino (N)-terminus in vitro. These results suggest that the phosphorylation of SERT by PKC-$\varepsilon$ may regulate SERT activity in plasma membrane.
Keywords
Serotonin; serotonin transporter; PKC-$\varepsilon$; protein-protein interaction; phosphorylation;
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