Abstract
Regulation of N-methyl-D-aspartate (NMDA) receptor activity by kinases and phosphatases contributes to the modulation of synaptic transmission. Targeting of these enzymes near the substrate is proposed to enhance phosphorylation-dependent modulation. Yotiao, an NMDA receptor-associated protein, bound the type I protein phosphatase (PP1) and the adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) holoenzyme. Anchored PP1 was active, limiting channel activity, whereas PKA activation overcame constitutive PP1 activity and conferred rapid enhancement of NMDA receptor currents. Hence, yotiao is a scaffold protein that physically attaches PP1 and PKA to NMDA receptors to regulate channel activity.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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A Kinase Anchor Proteins
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Binding Sites
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Carrier Proteins / metabolism*
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Cell Line
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Cyclic AMP / analogs & derivatives
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Cyclic AMP / pharmacology
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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Cytoskeletal Proteins / metabolism*
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Enzyme Inhibitors / pharmacology
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Holoenzymes / metabolism
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Humans
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Molecular Sequence Data
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Okadaic Acid / pharmacology
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Patch-Clamp Techniques
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Peptide Fragments / pharmacology
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Phosphoprotein Phosphatases / metabolism*
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Phosphorylation
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Rats
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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Thionucleotides / pharmacology
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Transfection
Substances
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A Kinase Anchor Proteins
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AKAP9 protein, human
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Adaptor Proteins, Signal Transducing
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Akap9 protein, rat
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Carrier Proteins
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Cytoskeletal Proteins
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Enzyme Inhibitors
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Holoenzymes
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Peptide Fragments
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Receptors, N-Methyl-D-Aspartate
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Recombinant Fusion Proteins
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Thionucleotides
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protein kinase inhibitor peptide (5-24)
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Okadaic Acid
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8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Phosphoprotein Phosphatases