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The Journal of Neuroscience, May 15, 2002, 22(10):3855-3863
Modulation of Drosophila Slowpoke
Calcium-Dependent Potassium Channel Activity by Bound Protein Kinase A
Catalytic Subunit
Yi
Zhou,
Jing
Wang,
Hua
Wen,
Olga
Kucherovsky, and
Irwin B.
Levitan
Department of Neuroscience, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania 19104
Drosophila Slowpoke (dSlo) calcium-dependent
potassium channels bind directly to the catalytic subunit of
cAMP-dependent protein kinase (PKAc). We demonstrate here that
coexpression of PKAc with dSlo in mammalian cells results in a dramatic
decrease of dSlo channel activity. This modulation requires
catalytically active PKAc but is not mediated by phosphorylation of
S942, the only PKA consensus site in the dSlo C-terminal domain.
dSlo binds to free PKAc but not to the PKA holoenzyme that includes
regulatory subunits and is inactive. Activators of endogenous PKA that
stimulate dSlo phosphorylation, but do not produce detectable PKAc
binding to dSlo, do not modulate channel function. Furthermore, the
catalytically inactive PKAc mutant does bind to dSlo but does not
modulate channel activity. These results are consistent with the
hypothesis that both binding of active PKAc to dSlo and phosphorylation
of dSlo or some other protein are necessary for channel modulation.
Key words:
Ca2+-dependent K+
channel; dSlo; cAMP-dependent protein kinase; protein-protein
interaction; phosphorylation; whole-cell recording; modulation
Copyright © 2002 Society for Neuroscience 0270-6474/02/22103855-09$05.00/0
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