Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postsynaptic density (PSD) fractions were isolated from the cerebral cortices of control and kindled rats and assayed for glutamate and gamma-aminobutyric acid-binding capacities and for the Ca2+/calmodulin-dependent protein kinase. Glutamate binding was found to be increased by approximately 50% in the PSDs isolated from kindled rats as compared to controls; this increase was almost completely from an increase in Bmax; Kd decreased only slightly. Studies with inhibitors indicate that the receptors involved were of the N-methyl-D-aspartate and quisqualate types. PSDs isolated from control and kindled rats did not differ in gamma-aminobutyric acid or flunitrazepam binding. The in vitro autophosphorylation of the Ca2+/calmodulin-dependent protein kinase was depressed by 45-76% in PSDs isolated from kindled rats as compared to controls, with little change in amount of the kinase. Therefore, we infer that (i) the kindled state is associated with an increase in glutamate activation of postsynaptic sites, allowing Ca2+ to enter dendritic spines, (ii) a change has occurred in activity of the protein kinase, which is the major cerebral cortex PSD protein, and (iii) perhaps major alterations in the PSD are a concomitant to the long-lasting nature of the kindled state.
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PMID:Effect of septal kindling on glutamate binding and calcium/calmodulin-dependent phosphorylation in a postsynaptic density fraction isolated from rat cerebral cortex. 216 74

The association of soluble Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) with postsynaptic densities (PSDs) was determined by activity assay, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblotting of the enzyme. Soluble CaM kinase II was autophosphorylated with ATP in the presence of Ca2+ and calmodulin, and then it was incubated with PSDs. Autophosphorylated CaM kinase II was precipitated with PSDs by centrifugation. The kinase that was not autophosphorylated did not precipitate with PSDs. These results indicate that the soluble previously autophosphorylated CaM kinase II associates with PSDs and forms PSD-CaM kinase II complex. A maximum of about 60 microg of soluble CaM kinase II bound to 1 mg of PSD protein under the experimental conditions. Ca2+-independent activity generated by autophosphorylation of the kinase was retained in the PSD-CaM kinase II complex. The CaM kinase II thus associated with PSDs phosphorylated a number of PSD proteins in both the absence and presence of Ca2+. When the CaM kinase II-PSD complex was incubated at 30 degrees C, its Ca2+-independent activity was gradually decreased. This decrease was correlated with dephosphorylation of the kinase and its release from PSD-CaM kinase II complex. These results indicate that CaM kinase II reversibly translocates to PSDs in a phosphorylation-dependent manner.
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PMID:Phosphorylation-dependent reversible association of Ca2+/calmodulin-dependent protein kinase II with the postsynaptic densities. 933 8

Ca2+ influx through N-methyl-D-aspartate- (NMDA-) type glutamate receptors plays a critical role in synaptic plasticity in the brain. One of the proteins activated by the increase in Ca2+ is CaM kinase II (CaMKII). Here, we report a novel synaptic Ras-GTPase activating protein (p135 SynGAP) that is a major component of the postsynaptic density, a complex of proteins associated with synaptic NMDA receptors. p135 SynGAP is almost exclusively localized at synapses in hippocampal neurons where it binds to and closely colocalizes with the scaffold protein PSD-95 and colocalizes with NMDA receptors. The Ras-GTPase activating activity of p135 SynGAP is inhibited by phosphorylation by CaMKII located in the PSD protein complex. Inhibition of p135 SynGAP by CaMKII will stop inactivation of GTP-bound Ras and thus could result in activation of the mitogen-activated protein (MAP) kinase pathway in hippocampal neurons upon activation of NMDA receptors.
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PMID:A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II. 962 Jun 94

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is localized in the postsynaptic density (PSD) and is necessary for LTP induction. Much has been learned about the autophosphorylation of CaMKII and its dephosphorylation by PSD protein phosphatase-1 (PP1). Here, we show how the CaMKII/PP1 system could function as an energy-efficient, bistable switch that could be activated during LTP induction and remain active despite protein turnover. We also suggest how recently discovered binding interactions could provide a structural readout mechanism: the autophosphorylated state of CaMKII binds tightly to the NMDAR and forms, through CaMKII-actinin-actin-(4.1/SAP97) linkages, additional sites for anchoring AMPARs at synapses. The proposed model has substantial experimental support and elucidates principles by which a local protein complex could produce stable information storage and readout.
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PMID:A model of synaptic memory: a CaMKII/PP1 switch that potentiates transmission by organizing an AMPA receptor anchoring assembly. 1150 52