Abstract
THE protein IsK (Mr 14,500) is present in epithelial cells1, heart2,3, uterus4 and lymphocytes5 and induces slowly activating K+ currents when expressed in Xenopus oocytes1. The finding that mutations of its single transmembrane segment altered channel gating6 or selectivity7 has suggested that IsK is a channel-forming protein. But IsK does nof exhibit the K+ channel hallmarks8 (a conserved K+ selective pore (H5) flanked by either six9–11 or two12,13 membrane-spanning regions). Here we report that IsK expression in Xenopus oocytes also induces a Cl− selective current very similar to the Cl− current produced by phospholemman expression14 and with biophysical, pharmacological and regulation characteristics very different from those of the IsK-induced K+ channel activity. IsK mutagenesis identifies amino- and carboxy-terminal domains as critical for the induction of Cl− and K+ channel activities, respectively. Our data lead to a model in which the IsK protein (now called IsK, Cl) acts as a potent activator of endogenous and otherwise silent K+ or Cl− channels.
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References
Takumi, T., Ohkubo, H. & Nakanishi, S. Science 242, 1042–1045 (1988).
Honore, E. et al. EMBO J. 10, 2805–2811 (1991).
Folander, K. et al. Proc. natn. Acad. Sci. U.S.A. 87, 2975–2979 (1990).
Pragnell, M. et al. Neuron 4, 807–812 (1990).
Attali, B. et al. J. biol. Chem. 267, 8650–8657 (1992).
Takumi, T. et al. J. biol. Chem. 266, 22192–22198 (1991).
Goldstein, S. A. N. & Miller, C. Neuron 7, 403–408 (1991).
Aldrich, R. Nature 362, 107–108 (1993).
Jan, L. Y. & Jan, Y. N. A. Rev. Physiol 54, 535–555 (1992).
Pongs, O. Physiol. Rev. 72, S69–S88 (1992).
Rudy, B., Kentros, C. & Vega-Saenz De Miera, E. Molec. cell. Neurosci. 2, 89–102 (1991).
Ho, K. et al. Nature 362, 31–38 (1993).
Kubo, Y., Baldwin, T. J., Jan, Y. N. & Jan, L. Y. Nature 362, 127–133 (1993).
Moorman, J. R., Palmer, C. J., John, J. E., Durieux, M. E. & Jones, L. R. J. biol. Chem. 267, 14551–14554 (1992).
Kreig, P. A. & Melton, D. A. Nucleic Acids Res. 12, 7057–7070 (1984).
Murai, T., Kazikuka, A., Takumi, T., Ohkubo, H. & Nakanishi, S. Biochem. biophys. Res. Commun. 161, 176–181 (1989).
Busch, A. E., Varnum, M., Adelman, J. P. & North, R. A. Biochem. biophys. Res. Commun. 184, 804–810 (1992).
Honoré, E., Attali, B., Lesage, F., Barhanin, J. & Lazdunski, M. Biochem. biophys,. Res. Commun. 184, 1135–1141 (1992).
Busch, A. E., Varnum, M. D., North, R. A. & Adelman, J. P. Science 255, 1705–1707 (1992).
Lesage, F. et al. Receptors Channels 1, 143–152 (1993).
Palmer, C. J., Scott, B. T. & Jones, L. R. J. biol. Chem. 266, 11126–11130 (1991).
Guillemare, E. et al. Biochemistry 31, 12463–12468 (1992).
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Attali, B., Guillemare, E., Lesage, F. et al. The protein IsK is a dual activator of K+ and CI− channels. Nature 365, 850–852 (1993). https://doi.org/10.1038/365850a0
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DOI: https://doi.org/10.1038/365850a0
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