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More Than a Scaffold

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Science  03 Dec 2004:
Vol. 306, Issue 5702, pp. 1653
DOI: 10.1126/science.306.5702.1653b

Yotiao is an anchoring protein that, in the heart, mediates the formation of a complex consisting of the IKs channel (a subunit KCNQ1 and regulatory subunit KCNE1), protein kinase A (PKA), and protein phosphatase 1 (PP1). Mutations that disrupt this complex interfere with the cardiac response to stress and can cause death. The effect of PKA on the channel can be mimicked by a mutation (S97D) in the KCNQ1 subunit. Using cells transfected with this mutant channel, Kurokawa et al. demonstrated that interaction with Yotiao increased channel current by slowing channel deactivation in the absence of cAMP. This effect was not blocked by inhibitors of PKA or protein kinase C, indicating that Yotiao was not promoting phosphorylation. Conversely, Yotiao did not alter wild-type channel kinetics in the absence of cAMP, which suggests that Yotiao not only promotes PKA phosphorylation of the channel but may also exert subsequent phosphorylation-dependent effects on channel deactivation kinetics. — NG

Proc. Natl. Acad. Sci. U.S.A. 101, 16374 (2004).

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