論文 - 詳細
| RRC ID | 39004 |
|---|---|
| 著者 | Sakai N, Sasaki K, Nakashita M, Honda S, Ikegaki N, Saito N. |
| タイトル | Modulation of serotonin transporter activity by a protein kinase C activator and an inhibitor of type 1 and 2A serine/threonine phosphatases. |
| ジャーナル | J Neurochem |
| Abstract |
We studied the effects of 12-O-tetradecanoylphorbol 13-acetate (TPA), a protein kinase C (PKC) activator, and calyculin A (CLA), an inhibitor of type 1 and 2A serine/threonine phosphatases, on serotonin uptake by a human placenta choriocarcinoma cell line (BeWo) and COS-7 cells expressing recombinant serotonin transporter (SET). In BeWo cells, treatment with TPA decreased imipramine-sensitive serotonin uptake with a reduction in Vmax without affecting Km. CLA also decreased imipramine-sensitive serotonin uptake in a manner similar to that of TPA. TPA and CLA also decreased the uptake activity of recombinant SET expressed in COS-7 cells as seen in BeWo cells. These effects of TPA and CLA were reversed by staurosporine, a protein kinase inhibitor. To elucidate whether the inhibitory effects of TPA and CLA were due to direct phosphorylation of SET by PKC, site-directed mutagenesis of five putative PKC phosphorylation sites in SET was performed. Serotonin uptake was also down-regulated by TPA and CLA in all nine mutants, suggesting that these inhibitory modulation of SET activity did not act via direct phosphorylation of SET by PKC. |
| 巻・号 | 68(6) |
| ページ | 2618-24 |
| 公開日 | 1997-6-1 |
| DOI | 10.1046/j.1471-4159.1997.68062618.x |
| PMID | 9166760 |
| MeSH | Adrenergic Uptake Inhibitors / pharmacology Animals COS Cells / chemistry COS Cells / enzymology Carcinogens / pharmacology Carrier Proteins / genetics Carrier Proteins / metabolism* Choriocarcinoma Humans Imipramine / pharmacology Marine Toxins Membrane Glycoproteins / genetics Membrane Glycoproteins / metabolism* Membrane Transport Proteins* Mutagenesis, Site-Directed / physiology Nerve Tissue Proteins* Oxazoles / pharmacology Phosphoprotein Phosphatases / antagonists & inhibitors* Protein Kinase C / metabolism* Protein Phosphatase 1 Rats Serotonin / metabolism Serotonin / pharmacokinetics Serotonin Plasma Membrane Transport Proteins Tetradecanoylphorbol Acetate / pharmacology Time Factors Transfection Tritium Tumor Cells, Cultured / chemistry Tumor Cells, Cultured / enzymology |
| IF | 4.066 |
| 引用数 | 53 |
| WOS 分野 | NEUROSCIENCES BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | COS-7(RCB0539) |