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)

This manuscript examines the mechanisms by which Ca2+/calmodulin-dependent protein kinase IV (CaM-kinase IV) is activated through the binding of Ca2+/CaM and by phosphorylation. Studies with the synthetic autoinhibitory domain peptides of CaM-kinase II indicate that CaM-kinase IV has a similarly located autoinhibitory domain, and this was confirmed since site-directed mutagenesis of this region (HMDT308 to DEDD and FN317 to DD) generated fully active Ca2+/CaM-independent kinases. Total activities of purified, baculovirus-expressed wild type and mutant kinases were increased 2-fold by intramolecular autophosphorylation, but this reaction was extremely slow (1-2 h) and probably not physiological. However, CaM-kinase IV can be activated by brain CaM-kinase IV kinase resulting in large increases in both total (5-7-fold) and Ca2+/CaM-independent (> 20-fold) CaM-kinase IV activities. This activation reaction required Mg2+/ATP and Ca2+/CaM, was intermolecularly catalyzed, and was reversed by protein phosphatase 2A. Activation of CaM-kinase IV resulted in a 10-fold decrease in Km for syntide-2 with little effect on Km for ATP or Vmax. CaM-kinase IV kinase was highly purified from rat brain extract and was shown to be a 68-kDa monomer. The results of this study demonstrate that CaM-kinase IV does have an autoinhibitory domain within residues His305-Lys321 that suppresses kinase activity in the absence of Ca2+/CaM. CaM-kinase IV is not significantly activated by autophosphorylation, but it can be activated 10-fold by a CaM-kinase IV kinase. This kinase cascade activation mechanism may be important for the physiological function of CaM-kinase IV such as transcriptional regulation through phosphorylation of cAMP responsive element binding protein (Enslen, H., Sun, P., Brickey, D., Soderling, S. H., Klamo, E., and Soderling, T.R. (1994) J. Biol. Chem. 269, 15520-15527).
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PMID:Activation mechanisms for Ca2+/calmodulin-dependent protein kinase IV. Identification of a brain CaM-kinase IV kinase. 796 13

To investigate the molecular mechanisms of stimuli-induced transcriptional activation in neuronal cells, we have investigated the light-induced gene expression in the neural retina of rats. The immunoreactivity for phosphorylated cAMP responsive element binding protein (PCREB-IR) was expressed in the outer half of the inner nuclear layer (INL) and the ganglion cell layer (GCL) after 5 min exposure to steady light also in mice. In addition to these cells, PCREB-IR was also detected in the inner border of the INL after 5 min exposure to flashing light. Both steady and flashing lights induced c-fos mRNA in the same types of cells as the PCREB-IR-positive cells. Majority of PCREB immunoreactive nuclei in the outer half of the INL were also immunopositive for anti-protein kinase C alpha (PKC alpha), a marker of rod bipolar cells, while CaM kinase IV immunoreactivity was not detected in these cells. PCREB-IR and c-fos gene expression in the PKC alpha positive rod bipolar cells were lost in mice lacking metabotropic glutamate receptor 6 (mGluR6). Thus, we propose that the transcriptional response of CREB to light stimulation in rod bipolar cells is regulated via mGluR6.
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PMID:CREB-induced transcriptional activation depends on mGluR6 in rod bipolar cells. 967 22

To define the molecular basis of alcohol drinking behaviors, the effects of voluntary ethanol intake on the expression of Ca(2+)/calmodulin-dependent protein kinase IV (CaM kinase IV) and on the expression and phosphorylation of cAMP responsive element binding protein (CREB) [corrected] in the nucleus accumbens (NAc), central amygdala, and frontal cortex of rats were investigated. Voluntary ethanol intake significantly decreased the expression of CaM kinase IV and CREB phosphorylation but not of CREB protein levels [corrected], specifically in the shell of NAc. These changes were not observed in the core of NAc, central amygdala and frontal cortex. Mianserin treatment significantly attenuated ethanol intake and antagonized the voluntary ethanol-induced reduction in expression of CaM kinase IV and CREB phosphorylation in the shell of NAc. This is the first evidence to suggest that decreased CaM kinase IV-dependent CREB phosphorylation in the shell region of NAc may play a role in the reward mechanisms of alcohol drinking.
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PMID:Effects of voluntary ethanol intake on the expression of Ca(2+) /calmodulin-dependent protein kinase IV and on CREB expression and phosphorylation in the rat nucleus accumbens. 1174 52