RGD Reference Report - Cyclic AMP-independent up-regulation of the human serotonin transporter by staurosporine in choriocarcinoma cells. - Rat Genome Database

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Cyclic AMP-independent up-regulation of the human serotonin transporter by staurosporine in choriocarcinoma cells.

Authors: Ramamoorthy, J D  Ramamoorthy, S  Papapetropoulos, A  Catravas, J D  Leibach, F H  Ganapathy, V 
Citation: Ramamoorthy JD, etal., J Biol Chem. 1995 Jul 21;270(29):17189-95. doi: 10.1074/jbc.270.29.17189.
RGD ID: 38500207
Pubmed: PMID:7615516   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.270.29.17189   (Journal Full-text)

Treatment of confluent cultures of JAR human placental choriocarcinoma cells with staurosporine caused a marked stimulation of serotonin transport activity in these cells. The stimulatory effect was noticeable at nanomolar concentrations of staurosporine, and a treatment time of > 4 h was required for staurosporine to elicit the effect. At 40 nM and with a treatment time of 16 h, the stimulation of the transport activity was 3.5-6.0-fold. None of the several other protein kinase inhibitors tested had similar effect except KT 5720, a protein kinase A inhibitor, which showed a small but significant (approximately 1.4-fold) stimulatory effect at a concentration of 5 microM. Blockade of RNA synthesis and protein synthesis in the cells prevented completely the stimulation of the transport activity induced by staurosporine. The stimulation was observed not only in intact cells but also in plasma membrane vesicles prepared from staurosporine-treated cells. The stimulation was accompanied by a 5-7-fold increase in the steady state levels of the transporter-specific mRNAs, by a 7-fold increase in the maximal velocity of the transport process, and by a 6-fold increase in the transporter density in the plasma membrane. Even though both staurosporine and cholera toxin had similar effects on the serotonin transport activity in these cells, the effect was not additive when the cells were treated with both reagents together. While treatment of the cells with cholera toxin markedly elevated intracellular levels of cAMP, staurosporine did not have any effect on the cellular levels of this cyclic nucleotide. It is concluded that staurosporine up-regulates the serotonin transport activity in JAR cells by increasing the steady state levels of the serotonin transporter mRNA and by the consequent increase in the transporter density in the plasma membrane and that the process involves a cAMP-independent signaling pathway.

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
staurosporine increases activityEXP 38500207staurosporine increases activity of SLC6A4 protein in placental choriocarcinoma cellsRGD 
staurosporine increases activityISOSLC6A4 (Homo sapiens)38500207; 38500207staurosporine increases activity of SLC6A4 protein in placental choriocarcinoma cellsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc6a4  (solute carrier family 6 member 4)

Genes (Mus musculus)
Slc6a4  (solute carrier family 6 (neurotransmitter transporter, serotonin), member 4)

Genes (Homo sapiens)
SLC6A4  (solute carrier family 6 member 4)


Additional Information