TY - JOUR
T1 - Functional link between tyrosine phosphorylation and human serotonin transporter gene expression
AU - Prasad, Puttur D.
AU - Torres-Zamorano, Viviana
AU - Kekuda, Ramesh
AU - Leibach, Frederick H.
AU - Ganapathy, Vadivel
N1 - Funding Information:
This work was supported by the National Institutes of Health Grant DA 10045. The authors thank Sarah Taylor and Ida O. Walker for expert secretarial assistance.
PY - 1997/4/23
Y1 - 1997/4/23
N2 - 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.
AB - 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.
KW - 5-HT (5-hydroxytryptamine, serotonin) transporter
KW - Choriocarcinoma cell, human
KW - Transcription
KW - Tyrosine kinase inhibitor
KW - Tyrosine phosphorylation
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U2 - 10.1016/S0014-2999(97)00100-3
DO - 10.1016/S0014-2999(97)00100-3
M3 - Article
C2 - 9151943
AN - SCOPUS:0030964057
SN - 0014-2999
VL - 325
SP - 85
EP - 92
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -