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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sterling, H. Ali, S. Wang, W. H. Dong, K. Gu, R. Huang, X. Y. Hebert, S. C. Wei, Y. Moral, Z. Giebisch, G. Deng, H. |
| Description | Author Affiliation: Moral Z ( Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.) |
| Abstract | We have used the two-electrode voltage clamp technique and the patch clamp technique to investigate the regulation of ROMK1 channels by protein-tyrosine phosphatase (PTP) and protein-tyrosine kinase (PTK) in oocytes coexpressing ROMK1 and cSrc. Western blot analysis detected the presence of the endogenous PTP-1D isoform in the oocytes. Addition of phenylarsine oxide (PAO), an inhibitor of PTP, reversibly reduced K(+) current by 55% in oocytes coinjected with ROMK1 and cSrc. In contrast, PAO had no significant effect on K(+) current in oocytes injected with ROMK1 alone. Moreover, application of herbimycin A, an inhibitor of PTK, increased K(+) current by 120% and completely abolished the effect of PAO in oocytes coexpressing ROMK1 and cSrc. The effects of herbimycin A and PAO were absent in oocytes expressing the ROMK1 mutant R1Y337A in which the tyrosine residue at position 337 was mutated to alanine. However, addition of exogenous cSrc had no significant effect on the activity of ROMK1 channels in inside-out patches. Moreover, the effect of PAO was completely abolished by treatment of oocytes with 20% sucrose and 250 microg/ml concanavalin A, agents that inhibit the endocytosis of ROMK1 channels. Furthermore, the effect of herbimycin A is absent in the oocytes pretreated with either colchicine, an inhibitor of microtubules, or taxol, an agent that freezes microtubules. We conclude that PTP and PTK play an important role in regulating ROMK1 channels. Inhibiting PTP increases the internalization of ROMK1 channels, whereas blocking PTK stimulates the insertion of ROMK1 channels. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 10 |
| Volume Number | 276 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2001-03-09 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Potassium Channels, Inwardly Rectifying Potassium Channels Metabolism Protein Tyrosine Phosphatases Protein-Tyrosine Kinases Alanine Chemistry Animals Benzoquinones Blotting, Western Colchicine Pharmacology Concanavalin A Enzyme Inhibitors Lactams, Macrocyclic Microscopy, Fluorescence Microtubules Models, Biological Mutation Oocytes Paclitaxel Patch-Clamp Techniques Potassium Quinones RNA, Complementary Rifabutin Analogs & Derivatives Sucrose Time Factors Tyrosine Xenopus Research Support, U.S. Gov't, P.H.S. Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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