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

To investigate the mechanism by which Drosophila generates multiple calcium/calmodulin-dependent protein kinase II (CaM kinase) subunits, CaM kinase cDNAs were isolated and sequenced. Eight different cDNA sequences, varying only at the junction of the regulatory and association domains of the kinase, were obtained. These results indicate that the diversity of CaM kinase in Drosophila is greater than previously appreciated and is generated by alternative splicing of a single gene. In situ hybridization showed CaM kinase mRNA is present in both neuronal and nonneuronal tissues in adult Drosophila. No differential tissue distribution of isoforms was observed.
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PMID:The diversity of calcium/calmodulin-dependent protein kinase II isoforms in Drosophila is generated by alternative splicing of a single gene. 839 98

Isoforms of calcium/calmodulin-dependent protein kinase II from Drosophila (R1-R6 and R3A) showed differential activation by two series of mutant calmodulins, B1K-B4K and B1Q-B4Q. These mutant calmodulins were generated by changing a glutamic acid in each of the four calcium binding sites to either glutamine or lysine, altering their calcium binding properties. All mutations produced activation defects, with the binding site 4 and B1Q mutants the most severe. Activation differed substantially between isoforms. R4, R5, and R6 were the least sensitive to mutations in calmodulin, while R1, R3, and R3A were the most sensitive. Activation of R1 and R2 by B4K and activation of R3 and R3A by B2K and B2Q produced significant (6-fold and almost 3-fold, respectively) differences in Kact between isoforms that differ structurally by a single amino acid. These differences could not be accounted for by differential binding, as all isoforms showed almost identical binding patterns with the mutants. High binding affinity did not always correlate with ability to increase enzyme activity, implying that activation occurs in at least two steps. The isoform-specific differences seen in this study reflect a role for the COOH-terminal variable region in activation of CaM kinase II.
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PMID:Functional diversity of alternatively spliced isoforms of Drosophila Ca2+/calmodulin-dependent protein kinase II. A role for the variable domain in activation. 870 94

The promoter region of the alpha-subunit of the calcium/calmodulin-dependent protein kinase II (alpha-CaMKII) gene was inserted into a beta-galactosidase (beta-gal) reporter plasmid, and beta-gal activities were examined in neuroblastoma (NB2a) and pheochromocytoma (PC12) cells after transient or stable transfections. The alpha-CaMKII promoter was 12- to 45-fold more active in NB2a compared with PC12 cells after transient or stable transfections. All-trans retinoic acid (RA) stimulated reporter gene expression at both protein and mRNA levels in transfected PC12 cells. RA increased the level of endogenous alpha-CaMKII mRNA in untransfected PC12 cells by 4.4-fold. The transcription initiation site(s) (TIS) of the alpha-CaMKII gene in PC12 cells and rat brain was examined by RNase protection assays (RPA) and reverse transcriptase PCRs. The TIS for the alpha-CaMKII/beta-gal reporter gene in transfected PC12 cells was indistinguishable from the TIS+1 in rat hippocampus. In contrast, the only detectable TIS for the alpha-CaMKII gene in untransfected PC12 cells was located near the ATG translation start codon, 147 nucleotides 3' to TIS+1 in hippocampus. This unusual TIS was also the predominant TIS in rat cerebellum. These results suggest that the alpha-CaMKII promoter may contain sequences that respond directly or indirectly to RA. In addition, the unusual TIS of the alpha-CaMKII gene in PC12 cells and rat cerebellum may contribute to the very low expression of this gene compared with that in hippocampus.
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PMID:Retinoic acid stimulates alpha-CAMKII gene expression in PC12 cells at a distinct transcription initiation site. 879 26

The recent characterization of plasticity in the mouse visual cortex permits the use of mutant mice to investigate the cellular mechanisms underlying activity-dependent development. As calcium-dependent signaling pathways have been implicated in neuronal plasticity, we examined visual cortical plasticity in mice lacking the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha CaMKII). In wild-type mice, brief occlusion of vision in one eye during a critical period reduces responses in the visual cortex. In half of the alpha CaMKII-deficient mice, visual cortical responses developed normally, but visual cortical plasticity was greatly diminished. After intensive training, spatial learning in the Morris water maze was severely impaired in a similar fraction of mutant animals. These data indicate that loss of alpha CaMKII results in a severe but variable defect in neuronal plasticity.
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PMID:Deficient plasticity in the primary visual cortex of alpha-calcium/calmodulin-dependent protein kinase II mutant mice. 881 12

The Type 3 inositol 1,4,5-trisphosphate (InsP3) receptor is expressed at high levels in gastrointestinal tissues. This receptor has 16 potential phosphorylation sites for calcium/calmodulin-dependent protein kinase II (CaM kinase II). To determine if the Type 3 InsP3 receptor is likely to be a physiologic substrate for CaM kinase II, localizations of the Type 3 InsP3 receptor and CaM kinase II were compared in tissues of the gastrointestinal tract. Cellular and subcellular localizations were determined by immunofluorescence microscopy in rat intestine, pancreas, and stomach, and in isolated rabbit gastric glands. Both proteins were found in the apical region of intestinal enterocytes, pancreatic acinar cells, and gastric parietal, chief, and surface mucous cells. CaM kinase II was found throughout the entire intracellular canalicular F-actin domain of parietal cells, whereas the type 3 InsP3 receptor was restricted to the neck region. Thus, in several gastrointestinal tissues the Type 3 InsP3 receptor is specifically localized to a portion of the apical cytoskeletal domain in which resides the calcium-responsive effector CaM kinase II.
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PMID:Co-distribution of calmodulin-dependent protein kinase II and inositol trisphosphate receptors in an apical domain of gastrointestinal mucosal cells. 891 99

Autophosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) at threonine-286 produces Ca2+-independent kinase activity and has been proposed to be involved in induction of long-term potentiation by tetanic stimulation in the hippocampus. We have used an immunocytochemical method to visualize and quantify the pattern of autophosphorylation of CaMKII in hippocampal slices after tetanization of the Schaffer collateral pathway. Thirty minutes after tetanic stimulation, autophosphorylated CaM kinase II (P-CaMKII) is significantly increased in area CA1 both in apical dendrites and in pyramidal cell somas. In apical dendrites, this increase is accompanied by an equally significant increase in staining for nonphosphorylated CaM kinase II. Thus, the increase in P-CaMKII appears to be secondary to an increase in the total amount of CaMKII. In neuronal somas, however, the increase in P-CaMKII is not accompanied by an increase in the total amount of CaMKII. We suggest that tetanic stimulation of the Schaffer collateral pathway may induce new synthesis of CaMKII molecules in the apical dendrites, which contain mRNA encoding its alpha-subunit. In neuronal somas, however, tetanic stimulation appears to result in long-lasting increases in P-CaMKII independent of an increase in the total amount of CaMKII. Our findings are consistent with a role for autophosphorylation of CaMKII in the induction and/or maintenance of long-term potentiation, but they indicate that the effects of tetanus on the kinase and its activity are not confined to synapses and may involve induction of new synthesis of kinase in dendrites as well as increases in the level of autophosphorylated kinase.
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PMID:Visualization of the distribution of autophosphorylated calcium/calmodulin-dependent protein kinase II after tetanic stimulation in the CA1 area of the hippocampus. 920 25

Previous studies have provided evidence for the presence of calcium/calmodulin-dependent protein kinase II (CaM kinase II) in rodent islets of Langerhans, and beta-cell CaM kinase II activity has been correlated with insulin secretion. In this study we provide the first conclusive evidence for the expression of CaM kinase II in human islets of Langerhans and show that multiple isoforms are expressed. Screening of a human islet cDNA library resulted in the isolation of a 999bp partial cDNA clone encoding CaM kinase II. The nucleotide sequence of the islet clone showed a high degree of homology (94.8%) to the two gamma isoforms of CaM kinase II previously isolated from human T lymphocytes (gammaB and gammaC). In order to obtain full length sequence for the islet clone, rapid amplification of cDNA ends (RACE) was used to amplify the 3' end of the islet clone from human islet poly A+ RNA. Two distinct gamma isoforms of CaM kinase II were amplified from the islet RNA. They were identified as gammaB and gammaE; the latter is distinguished from gammaB by a 114bp insertion within the association domain of the cDNA. Using reverse transcriptase polymerase chain reaction (RT-PCR) we also detected in human islets of Langerhans the novel beta3 isoform of CaM kinase II previously reported to be expressed in neonatal rat islets.
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PMID:Human islets of Langerhans express multiple isoforms of calcium/calmodulin-dependent protein kinase II. 924 Apr 63

The rat mu-opioid receptor (rMOR1), expressed in human embryonic kidney 293 (HEK293) cells, shows a desensitization to the inhibitory effect of the mu agonist DAMGO on adenylate cyclase activity within 4 h of DAMGO preincubation. To investigate the role of calcium/calmodulin-dependent protein kinase II (CaM kinase II) on mu-opioid receptor desensitization, we coexpressed rMOR1 and constitutively active CaM kinase II in HEK293 cells. This coexpression led to a faster time course of agonist-induced desensitization of the mu-opioid receptor. The increase of desensitization could not be observed with a mu-opioid receptor mutant (S261A/S266A) that lacks two putative CaM kinase II phosphorylation sites in the third intracellular loop. In addition, injection of CaM kinase II in Xenopus oocytes led only to desensitization of expressed rMOR1, but not of an S261A/S266A receptor mutant. These results suggest that phosphorylation of Ser261 and Ser266 by CaM kinase II is involved in the desensitization of the mu-opioid receptor.
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PMID:Site mutation in the rat mu-opioid receptor demonstrates the involvement of calcium/calmodulin-dependent protein kinase II in agonist-mediated desensitization. 932 7

In Drosophila, calcium/calmodulin-dependent protein kinase II (CaM kinase) has been shown to be important in the expression of both learning and memory for the associative behavior courtship conditioning. In this study we examine the role of visual input in producing this behavior and the effects of modifying visual input on CaM kinase-dependent memory formation. Inhibition of CaM kinase blocked apparent learning regardless of visual input. Visual input selectively affected the memory phase of courtship conditioning: normal visual input masked the memory effects of inhibition of CaM kinase resulting in generation of memory without apparent learning, whereas disruption of visual input revealed the CaM kinase-dependence of memory. Visual input was found to be important only during the training period, which implies that vision and CaM kinase are interacting in the formation rather than the retrieval of memory. Our results suggest a model for courtship conditioning in which multiple sensory inputs are integrated at a CaM-kinase-dependent neuronal switch to modulate courtship behavior.
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PMID:CaM kinase II and visual input modulate memory formation in the neuronal circuit controlling courtship conditioning. 936 84

In the present investigation, in vitro phosphorylation of CNS proteins of the silkworm Bombyx mori during the postembryonic development have been studied. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography of phosphorylated proteins revealed the presence of major phosphoproteins of 59/60 kDa. Based on molecular mass, calcium/calmodulin-dependent autophosphorylation, substrate specificity, KN-62 inhibition, apparent Km for ATP and syntide-2, these proteins were identified as calcium/calmodulin-dependent protein kinase II (CaM kinase II). Anti-rat CaM kinase II monoclonal antibody showed immunoreactivity with Bombyx CaM kinase II isoforms. This kinase showed a high degree of autophosphorylation in neural tissue. During postembryonic development of Bombyx, two distinct peaks of enzyme activity could be noticed, one at the late-larval and another at the late-pupal stage, which were associated with an increase in amount of the enzyme. These results suggested that the expression of CaM kinase II in the CNS of Bombyx was developmentally regulated.
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PMID:Identification, characterization, immunocytochemical localization, and developmental changes in the activity of calcium/calmodulin-dependent protein kinase II in the CNS of Bombyx mori during postembryonic development. 952 82


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