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Titolo:
Regulation of ROMK1 channels by protein-tyrosine kinase and -tyrosine phosphatase
Autore:
Moral, Z; Dong, K; Wei, Y; Sterling, H; Deng, H; Ali, SR; Gu, RM; Huang, XY; Hebert, SC; Giebisch, G; Wang, WH;
Indirizzi:
New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA New York Med Coll Valhalla NY USA 10595 Pharmacol, Valhalla, NY 10595 USA Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA Yale Univ New Haven CT USA 06510 r & Mol Physiol, New Haven, CT 06510 USA Cornell Univ, Coll Med, Dept Physiol, New York, NY 10021 USA Cornell UnivNew York NY USA 10021 , Dept Physiol, New York, NY 10021 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 10, volume: 276, anno: 2001,
pagine: 7156 - 7163
SICI:
0021-9258(20010309)276:10<7156:RORCBP>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
CORTICAL COLLECTING DUCT; POTASSIUM-CHANNEL; K+ CHANNEL; COUPLED RECEPTORS; BREFELDIN-A; PHOSPHORYLATION; SRC; MODULATION; ACTIVATION; SENSITIVITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Wang, WH New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA New York Med Coll Valhalla NY USA 10595 , Valhalla, NY 10595 USA
Citazione:
Z. Moral et al., "Regulation of ROMK1 channels by protein-tyrosine kinase and -tyrosine phosphatase", J BIOL CHEM, 276(10), 2001, pp. 7156-7163

Abstract

We have used the two-electrode voltage clamp technique and the patch clamptechnique 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 care. Theeffects 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 ROMX1 channels in inside-out patches. Moreover, the effect of PAO was completely abolished by treatment of oocytes with 20% sucrose and 250 mug/ml concanavalin A, agents that inhibit the endocytosis of ROMK1channels. Furthermore, the effect of herbimycin A is absent in the oocytespretreated 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.

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Documento generato il 31/10/20 alle ore 03:52:23