Disease relevance of Camk4

• When cDNA for rat brain CaM-kinase IV was expressed in Escherichia coli, the enzyme was produced in a good yield, but it did not show significant activity [1].
• Antisense CCDPK ODN treatment at 2 wk after injury resulted in a significant inhibition of intima hyperplasia, compared with untreated vessels [2].
• CONCLUSION: SPD protected striatal neurons against ischemic injury and antagonized the inhibitory action on CCDPK activity induced by ischemia [3].
• RESULTS: Under anoxia for 30 min, the CCDPK II activity decreased to 29.2% and 27.0% of the control in rat hippocampal and striatal slices, respectively [4].

Psychiatry related information on Camk4

• 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 [5].

High impact information on Camk4

• Calcium regulation of dendritic growth via CaM kinase IV and CREB-mediated transcription [6].
• Calcium-dependent dendritic growth is suppressed by CaM kinase inhibitors, a constitutively active form of CaM kinase IV induces dendritic growth in the absence of extracellular stimulation, and a kinase-dead form of CaM kinase IV suppresses dendritic growth induced by calcium influx [6].
• These mechanisms, which implicate CaM kinase IV and CREB in the control of BDNF expression, are likely to be centrally involved in activity-dependent plasticity during development [7].
• The portion of sequence that extended from the hypothesized calmodulin-binding domain to the carboxyl terminus of the protein was identical at both the amino acid and nucleotide level to the noncatalytic, calmodulin-binding protein calspermin from rat testis [8].
• The deduced amino acid sequence was confirmed by comparison with the peptide sequence from purified CaM kinase Gr [8].

Chemical compound and disease context of Camk4

• In the present study, rat CaM-kinase IV was expressed in Sf9 cells and Escherichia coli, and the kinetic properties were examined with syntide-2 and peptide-gamma as substrates [9].

Biological context of Camk4

• Screening a genomic library with a portion of the cDNA for CaM kinase Gr allowed the isolation of a genomic clone that contained at least 9 kilobases (kb) of the gene for CaM kinase Gr [8].
• In situ hybridization was used to demonstrate that both kinase and calspermin mRNAs are expressed during spermatogenesis [10].
• Calspermin mRNA first appears in pachytene primary spermatocytes and continues to increase as cells complete meiosis and undergo terminal differentiation [10].
• 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 [11].
• Analysis of cells isolated from rat testis reveals calspermin mRNA to be predominantly expressed in postmeiotic cells indicating that it may be specific to haploid cells [12].

Anatomical context of Camk4

• Although the transgene promoter was silent in somatic tissues, beta-galactosidase expression could be restored in primary cultures of skin fibroblasts by introduction of vectors encoding CREM tau and CaM kinase IV [13].
• On the other hand, ethanol treatment produced a significant reduction in the protein levels of CREB, p-CREB, and CaM kinase IV in the cingulate gyrus, and these changes reverted to normal levels during ethanol withdrawal [14].
• E2 also increased CaMK IV and pCREB immunolabeling in the CA1 and CA3 regions, but not CA2 region or dentate gyrus, of the hippocampus [15].
• However, the immunoreactivity was weak in the nuclei of the granule cells in the cerebellar cortex, although the nuclei of the granule cells were reported to contain high CaM-kinase IV activity [16].
• Calmodulin-dependent protein kinase IV (CaM-kinase IV) is thought to play crucial roles in the functioning of Ca2+ in the central nervous system and immune system, and the regulation of its activity is therefore very important [9].

Associations of Camk4 with chemical compounds

• 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 [11].
• Calspermin contains a stretch of 17 contiguous glutamic acid residues in the central region of the molecule [12].
• Replacement of Thr-196 of CaM kinase IV with a nonphosphorylatable alanine by site-directed mutagenesis abolishes both the phosphorylation and activation of CaM kinase IV, demonstrating that Thr-196 phosphorylation is essential for activation [17].
• The initial phosphorylation occurred in the amino-terminal serine-rich region of CaM-kinase IV [18].
• Selective phosphorylation of nuclear CREB by fluoxetine is linked to activation of CaM kinase IV and MAP kinase cascades [19].

Enzymatic interactions of Camk4

• In parallel fashion to its activation, CaM kinase IV is phosphorylated in a CaM kinase Ia kinase-, Ca(2+)-CaM-, and MgATP-dependent manner [17].
• Present study revealed that CaMKK also phosphorylated CaM kinase IV associated with the activation of its activity [20].

Regulatory relationships of Camk4

• Rat brain calmodulin-dependent protein kinase IV (CaM-kinase IV) was activated approximately 20 to 30-fold by incubation with CaM-kinase IV kinase purified from rat brain under the Ca2+/calmodulin-dependent phosphorylation conditions [18].
• RESULTS: PD98059 inhibited bFGF-induced phosphorylation of CCDPK and DNA synthesis [21].
• In addition, CaM kinase I was activated in a lower concentration of glutamate than that of CaM kinase IV [22].
• Therefore, it appears that Ca2+ oscillations elicited by the high-affinity CCK-AR/Gbeta/cPLA2/AA pathway activate CaMK IV [23].
• RESULTS: PDGF-BB (2 micrograms.L-1) induced DNA synthesis and activated CCDPK in a concentration-dependent manner and a induced a marked c-myc mRNA expression [24].

Other interactions of Camk4

• CBP-mediated transcription is stimulus strength-dependent and can be induced by activation of CaM kinase II, CaM kinase IV, and protein kinase A, but not by activation of the Ras-MAP kinase pathway [25].
• Ca2+/calmodulin-dependent protein kinase enriched in cerebellar granule cells (CaM kinase Gr) is a neuronal calmodulin-dependent protein kinase whose purification and partial cloning from rat brain has been described [8].
• Calmodulin-dependent protein kinase IV (CaM-kinase IV), which plays crucial roles in the functioning of Ca2+ in the central nervous system and immune system, is markedly activated upon phosphorylation by the action of CaM-kinase IV kinase [26].
• CONCLUSION: The p42/p44-CCDPK antisense ODN inhibits in vitro stimulated rat VSMC proliferation and in vivo injured arterial intima hyperplasia [2].
• In contrary, 65% or 75% EGF- or tetradecanoylphorbol acetate (TDPA, formally called PMA)--stimulated CCDPK activity and 38% or 42% [3H]thymidine incorporation treated by PDBU were inhibited, respectively [27].

Analytical, diagnostic and therapeutic context of Camk4

• In addition, the purification by HPLC on DEAE-NPR revealed that a novel Ca(2+)-dependent calmodulin-binding protein, designated as CaMBP64, is present as a major contaminant in the previous purified CaM-kinase IV preparation [28].
• Caloric restriction significantly (P<0.05) reduced the age-related decline in CaN activity, but had no significant effect on CaMK-IV activity [29].
• Western blot analysis revealed increased protein levels of CaMK IV in the nuclear but not in the membranal or cystolic fraction of total amygdala in E2-treated compared to OVX rats [30].
• In immunoblotting analysis, a single band of 63 kDa was detected in the crude homogenate of the adult rat retina, indicating the presence of the alpha polypeptide of CaM kinase IV [31].
• Using the indirect immunofluorescence technique, the distribution of Ca2+/calmodulin-dependent protein kinase IV (CaM kinase IV) was studied in dorsal root ganglia (DRGs) and the sciatic nerve under normal circumstances and after axotomy and nerve ligation [32].

References