Coexpression of the catalytic subunit of cAMP-dependent protein kinase (PKAc) with Drosophila Slowpoke (dSlo) channels dramatically decreased dSlo channel activity.
Direct binding of active PKAc to the dSlo calcium-dependent potassium channel is necessary for the profound downregulation of its channel activity, independent of phosphorylation at the primary consensus site.
Absolute Event Rate: 708% vs 1807%
p-value: p=<0.001
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.
Zhou et al. (Wed,) reported a other. PKAc coexpression vs. dSlo expression alone was evaluated on Peak dSlo current density at +165 mV (pA/pF) (p=<0.001). Coexpression of the catalytic subunit of cAMP-dependent protein kinase (PKAc) with Drosophila Slowpoke (dSlo) channels dramatically decreased dSlo channel activity.
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