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)

Long-term potentiation (LTP) is an experimental model for memory and learning in higher animals. It is a well-known fact that intracellular rise in Ca2+ is an essential requirement for generation of LTP. Little is known about the synaptic modulation triggered by the intracellular Ca2+ rise, though the involvement of protein kinase C, Ca2+/calmodulin-dependent protein kinase II (CaM KII), and/or calpain are indicated experimentally. For the purpose of making the synaptic change clearer we tried to characterize the substrates for the protein kinases associated with isolated postsynaptic density (PSD)-enriched fractions. Four major groups of substrates for the CaM KII (250 k M(r), 200 k M(r), 180 k M(r), and 140 k M(r)) and one for kinase C (17 k M(r)) were identified. The 250 k M(r) substrate resembled P400 protein, IP3 receptor, in structure. The 17 k M(r) substrate was different from myelin basic protein which was electrophoresed nearly at the same distance. We made an antibody against the 140 k M(r) substrates to obtain biological and physicochemical properties of the protein. We also made an antibody specific to the Thr286-autophosphorylated and autonomous form of CaM KII. The latter antibody is an extremely useful reagent to understand the biological functions of the CaM KII, especially the role of autophosphorylation of the kinase in modulation of the synaptic function such as in LTP.
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PMID:[Postsynaptic mechanism of long-term potentiation]. 141 33

Purified P400 protein was phosphorylated by both purified Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) and the catalytic subunit of cyclic AMP-dependent protein kinase (A-kinase). Because P400 protein was suggested to function as an integral membrane protein, we investigated the phosphorylation of P400 protein using crude mitochondrial and microsomal fractions (P2/P3 fraction). Incubation of the P2/P3 fraction from mouse cerebellum with cyclic AMP or the catalytic subunit of A-kinase stimulated the phosphorylation of P400 protein. The phosphorylation of P400 protein was not observed in the P2/P3 fraction from mouse forebrain. Cyclic AMP and A-kinase enhanced the phosphorylation of several proteins, including P400 protein, suggesting that P400 protein is one of the best substrates for A-kinase in the P2/P3 fraction. Although endogenous and exogenous CaM kinase II stimulated the phosphorylation of some proteins in the P2/P3 fraction, the phosphorylation of P400 protein was weak. Immunoprecipitation with the monoclonal antibody to P400 protein confirmed that the P400 protein itself was definitely phosphorylated by the catalytic subunit of A-kinase and CaM kinase II. A-kinase phosphorylated only the seryl residue in P400 protein. Immunoblot analysis of the cells in primary culture of mouse cerebellum confirmed the expression of P400 protein, which migrated at the same position on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as that in the P2/P3 fraction. Incubation of the cultured cerebellar cells with [32P]orthophosphate resulted in the labeling of P400 protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phosphorylation of P400 protein by cyclic AMP-dependent protein kinase and Ca2+/calmodulin-dependent protein kinase II. 254 6