ArticleThe Journal of biological chemistry2011
Ca2+/calmodulin-dependent protein kinase II inhibitors disrupt AKAP79-dependent PKC signaling to GluA1 AMPA receptors.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- A revised view of the role of CaMKII in learning and memory.Nature neuroscience · 2025Review
- LTP expression mediated by autonomous activity of GluN2B-bound CaMKII.Cell reports · 2024Article
- Studying CaMKII: Tools and standards.Cell reports · 2024Review
- Article
- A Modeling and Analysis Study Reveals That CaMKII in Synaptic Plasticity Is a Dominant Affecter in CaM Systems in a T286 Phosphorylation-Dependent Manner.Molecules (Basel, Switzerland) · 2022Article
- Role of CaFrontiers in molecular neuroscience · 2022Review
- Spatiotemporal restriction of endothelial cell calcium signaling is required during leukocyte transmigration.The Journal of experimental medicine · 2021Article
- FRET-based sensor for CaMKII activity (FRESCA): A useful tool for assessing CaMKII activity in response to CaThe Journal of biological chemistry · 2019Article
- Preferential generation of CaThe Journal of biological chemistry · 2019Article
- CaMKII regulates the depalmitoylation and synaptic removal of the scaffold protein AKAP79/150 to mediate structural long-term depression.The Journal of biological chemistry · 2018Review
- Protein Kinase Cϵ (PKCϵ) Promotes Synaptogenesis through Membrane Accumulation of the Postsynaptic Density Protein PSD-95.The Journal of biological chemistry · 2016Article
- Article
- Protein Kinase C (PKC)ζ Pseudosubstrate Inhibitor Peptide Promiscuously Binds PKC Family Isoforms and Disrupts Conventional PKC Targeting and Translocation.Molecular pharmacology · 2015Article
- Excitotoxic glutamate insults block autophagic flux in hippocampal neurons.Brain research · 2014Article
- Signaling pathways involved in striatal synaptic plasticity are sensitive to temporal pattern and exhibit spatial specificity.PLoS computational biology · 2013Article
- Loss of Thr286 phosphorylation disrupts synaptic CaMKIIα targeting, NMDAR activity and behavior in pre-adolescent mice.Molecular and cellular neurosciences · 2011Article
- A kinase anchor protein 150 (AKAP150)-associated protein kinase A limits dendritic spine density.The Journal of biological chemistry · 2011Article
- CaMKII in cerebral ischemia.Acta pharmacologica Sinica · 2011Review
- Article
- PKC phosphorylates GluA1-Ser831 to enhance AMPA receptor conductance.Channels (Austin, Tex.)Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
GluA1 (formerly GluR1) AMPA receptor subunit phosphorylation at Ser-831 is an early biochemical marker for long-term potentiation and learning. This site is a substrate for Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) and protein kinase C (PKC). By directing PKC to GluA1, A-kinase anchoring protein 79 (AKAP79) facilitates Ser-831 phosphorylation and makes PKC a more potent regulator of GluA1 than CaMKII. PKC and CaM bind to residues 31-52 of AKAP79 in a competitive manner. Here, we demonstrate that common CaMKII inhibitors alter PKC and CaM interactions with AKAP79(31-52). Most notably, the classical CaMKII inhibitors KN-93 and KN-62 potently enhanced the association of CaM to AKAP79(31-52) in the absence (apoCaM) but not the presence of Ca(2+). In contrast, apoCaM association to AKAP79(31-52) was unaffected by the control compound KN-92 or a mechanistically distinct CaMKII inhibitor (CaMKIINtide). In vitro studies demonstrated that KN-62 and KN-93, but not the other compounds, led to apoCaM-dependent displacement of PKC from AKAP79(31-52). In the absence of CaMKII activation, complementary cellular studies revealed that KN-62 and KN-93, but not KN-92 or CaMKIINtide, inhibited PKC-mediated phosphorylation of GluA1 in hippocampal neurons as well as AKAP79-dependent PKC-mediated augmentation of recombinant GluA1 currents. Buffering cellular CaM attenuated the ability of KN-62 and KN-93 to inhibit AKAP79-anchored PKC regulation of GluA1. Therefore, by favoring apoCaM binding to AKAP79, KN-62 and KN-93 derail the ability of AKAP79 to efficiently recruit PKC for regulation of GluA1. Thus, AKAP79 endows PKC with a pharmacological profile that overlaps with CaMKII.
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