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(Circulation Research. 2004;94:1359.)
© 2004 American Heart Association, Inc.

Cellular Biology

Multisite Phosphorylation Mechanism for Protein Kinase A Activation of the Smooth Muscle ATP-Sensitive K⁺ Channel

Kathryn V. Quinn, Jonathan P. Giblin, Andrew Tinker

From the British Heart Foundation Laboratories and the Department of Medicine, University College London, UK.

Correspondence to Andrew Tinker, Department of Medicine, University College London, 5 University St, London WC1E 6JJ, UK. E-mail a.tinker{at}ucl.ac.uk

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.

Key Words: Kir6.1 • ATP-sensitive potassium channel • ion channel regulation • protein kinase A • protein phosphorylation

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