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PNAS 101 (46): 16374-16378

Copyright © 2004 by the National Academy of Sciences.

PHYSIOLOGY

Regulatory actions of the A-kinase anchoring protein Yotiao on a heart potassium channel downstream of PKA phosphorylation

Junko Kurokawa, Howard K. Motoike, Jenny Rao, and Robert S. Kass *

Department of Pharmacology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032

Edited by Ramon Latorre, Center for Scientific Studies, Valdivia, Chile, and approved October 4, 2004

Received for publication July 31, 2004.

Abstract: A-kinase anchoring proteins (AKAPs) are thought to be passive members of protein complexes that coordinate the association of cAMP-dependent protein kinase A (PKA) with cellular substrates to facilitate targeted PKA protein phosphorylation. IKs, the slow heart postassium current, is carried by the IKs potassium channel, a substrate for PKA phosphorylation in response to sympathetic nerve stimulation, is a macromolecular complex that includes the KCNQ1 {alpha} subunit, the KCNE1 regulatory subunit, and the AKAP Yotiao. Disruption of this regulation by mutation in the long QT syndrome is associated with elevated risk of sudden death. Here, we have studied the effects of the AKAP Yotiao on the function of the IKs channel that had been mutated to simulate channel phosphorylation, and we report direct AKAP-mediated alteration of channel function distinct from its role in the coordination of channel phosphorylation by PKA. These data reveal previously undescribed actions of Yotiao that occur subsequent to channel phosphorylation and provide evidence that this adaptor protein also may serve as an effector in regulating this important ion channel.

Key Words: adaptor • KCNQ1 • KCNE1

Author contributions: J.K. and R.S.K. designed research; J.K. performed research; H.K.M. and J.R. contributed new reagents/analytic tools; J.K. and R.S.K. analyzed data; and J.R. and R.S.K. wrote the paper.

This paper was submitted directly (Track II) to the PNAS office.

Freely available online through the PNAS open access option.

Abbreviations: AKAP, A-kinase anchoring protein; CHO, Chinese hamster ovary; LZ, leucine zipper; OA, okadaic acid; PKA, protein kinase A.

* To whom correspondence should be addressed. E-mail: rsk20{at}columbia.edu.

© 2004 by The National Academy of Sciences of the USA

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