Functional link between tyrosine phosphorylation and human serotonin transporter gene expression

Puttur D. Prasad, Viviana Torres-Zamorano, Ramesh Kekuda, Frederick H. Leibach, Vadivel Ganapathy

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Abstract

Treatment of the JAR human placental choriocarcinoma cells with herbimycin A, an inhibitor of tyrosine kinases, led to an increase in the activity of the serotonin transporter. This effect was accompanied by an increase in the serotonin transporter density and in the steady-state levels of the serotonin transporter mRNA. A treatment time of > 4 h was necessary for herbimycin A to elicit its effect. Actinomycin D and cycloheximide blocked the effect. There was no increase in the steady-state levels of the serotonin transporter mRNA when cells were treated with herbimycin A in the presence of actinomycin D. The herbimycin A-induced increase in the transporter activity was abolished by genistein, another inhibitor of tyrosine kinases. But the increase in the transporter mRNA levels caused by herbimycin A was not affected by genistein. Treatment of cells with herbimycin A resulted in an increase in the tyrosine phosphorylation of specific cellular proteins, suggesting that herbimycin A directly or indirectly activates specific tyrosine kinases. It is concluded that tyrosine phosphorylation is an essential component in the signaling pathways participating in the regulation of the human serotonin transporter gene expression.

Original languageEnglish (US)
Pages (from-to)85-92
Number of pages8
JournalEuropean Journal of Pharmacology
Volume325
Issue number1
DOIs
StatePublished - Apr 23 1997

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Keywords

  • 5-HT (5-hydroxytryptamine, serotonin) transporter
  • Choriocarcinoma cell, human
  • Transcription
  • Tyrosine kinase inhibitor
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Pharmacology

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