The study identifies specific phosphorylation sites on SUR2B and Kir6.1 subunits required for protein kinase A-mediated activation of vascular smooth muscle ATP-sensitive K+ channels.
May guide KATP modulator development; leaves open translation from animal data to human disease.
The activation of ATP-sensitive K+ channels by protein kinase A in vascular smooth muscle is an important component of the action of vasodilators. In this study, we examine the molecular mechanisms of regulation of the cloned equivalent of this channel comprising the sulfonylurea receptor 2B and the inward rectifier 6.1 subunit (SUR2B/Kir6.1). Specifically, we focus on whether the channel is directly phosphorylated and the sites at which this occurs in the protein complex. We identify one site in Kir6.1 (S385) and two sites in SUR2B (T633 and S1465) using a combination of biochemical and functional assays. Our work supports a model in which multiple sites in the channel complex have to be phosphorylated before activation occurs.
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Quinn et al. (2004) studied this question.
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