| Home | Organizers | Proceedings Editors | Proceedings Contributors | Search | | ||
|
|
|||
|
||||
|
|
||||
| Title: | HERG POTASSIUM CHANNEL IS REGULATED BY PROTEIN TYROSINE KINASE (PTK) IN HUMAN EMBRYONIC KIDNEY CELLS | |
| DOI No: | 10.1142/9789812702234_0009 | |
| Source: | ADVANCES IN ELECTROCARDIOLOGY 2004 (pp 54-56) | |
| Author(s): | LONG-MEI WU
Depts of Cardiovascular Diseases, Bio-infomatic pharmacology Medical Research, Institute, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Tokyo, Japan KAZUO UEDA Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Tokyo, Japan YUJI HIRANO Depts of Cardiovascular Diseases, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Tokyo, Japan TETSUSHI FURUKAWA Bio-Informatic Pharmacology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Tokyo, Japan MASAYASU HIRAOKA Depts of Cardiovascular Diseases, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Tokyo, Japan |
|
| Abstract: | Regulation of HERG potassium channel by protein tyrosine kinase (PTK), c-Src, was studied using heterologous expression system. Co-expression of HERG with constitutively active c-Src (Y530F) markedly decreased HERG current amplitudes, while kinase dead c-Src (K298M) did not change the current amplitude. Pre-incubation of PTK inhibitors (herbimycine A and PP2) restored decreased HERG current by c-Src (Y530F). Co-expression of c-Src (Y530F) shifted activation voltage of HERG current in a positive direction by 11 mV, but c-Src (K298M) did not induce such change. PTK inhibitors also restored voltage shift. Immunoblot analysis revealed that c-Src (Y530F) induced large retention of immature band of HERG protein, with much decreased mature band. Two forms of HERG protein were phosphorylated by c-Src (Y530F), but not by c-Src (K298M). Pre-treatment of PTK inhibitors decreased the retention of immature HERG protein and abolished phosphorylation. The results indicate that tyrosine phosphorylation by c-Src affects the maturation of HERG protein leading to trafficking defect to the plasma membrane, and decreases current amplitude with a shift in activation voltage of HERG channel current on the plasma membrane. | |
| Full Text: | View full text in PDF format (99KB) | |
| TOC: | Back to Table of Contents | |
|
||