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Distinct enzyme combinations in AKAP signalling complexes permit functional diversity.

Naoto Hoshi·Lorene K Langeberg·John D Scott
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Abstract

Specificity in cell signalling can be influenced by the targeting of different enzyme combinations to substrates. The A-kinase anchoring protein AKAP79/150 is a multivalent scaffolding protein that coordinates the subcellular localization of second-messenger-regulated enzymes, such as protein kinase A, protein kinase C and protein phosphatase 2B. We developed a new strategy that combines RNA interference of the endogenous protein with a protocol that selects cells that have been rescued with AKAP79/150 forms that are unable to anchor selected enzymes. Using this approach, we show that AKAP79/150 coordinates different enzyme combinations to modulate the activity of two distinct neuronal ion channels: AMPA-type glutamate receptors and M-type potassium channels. Utilization of distinct enzyme combinations in this manner provides a means to expand the repertoire of cellular events that the same AKAP modulates.

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Adaptor Proteins, Signal TransducingCalcineurinCalcineurin InhibitorsCarrier ProteinsCell LineCyclic AMP-Dependent Protein KinasesDiscs Large Homolog 1 ProteinHumansMembrane ProteinsMembrane Transport ProteinsModels, BiologicalMuscarinic AgonistsPotassium ChannelsRNA InterferenceSignal TransductionTime FactorsTransfectionalpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic AcidJournal ArticleResearch Support, N.I.H., Extramural

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Naoto Hoshi, Lorene K Langeberg, John D Scott. 2005. Distinct enzyme combinations in AKAP signalling complexes permit functional diversity.. https://doi.org/10.1038/ncb1315

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