Disease relevance of CAMK4

• We investigated the basis of CaM kinase-Gr expression in EBV-transformed cells and the mechanisms that regulate its activity therein by using an EBV-negative Burkitt lymphoma cell line, BJAB, and BJAB cells converted to expression of individual EBV proteins by single-gene transfer [1].
• Western blot analysis, using a polyclonal antibody raised against the recombinant human CaM-kinase IV, which was expressed in Escherichia coli, revealed two bands corresponding in mobility to molecular weights of 60,000 and 61,000, respectively, in a Jurkat cell extract [2].
• We conclude that magnesium sulfate administration prior to hypoxia prevents hypoxia-induced increase in CaM Kinase IV and Protein Tyrosine Kinase activities [3].

High impact information on CAMK4

• It is initiated by a highly local, rise in calcium ion concentrations near the cell membrane, but culminates in the activation of a specific calmodulin-dependent kinase known as CaMK IV, which is constitutively present in the neuronal nucleus [4].
• Multifunctional Ca2+/calmodulin-dependent (CaM) kinase, CaM kinase Ia, CaM kinase Ib and CaM kinase IV are four of the kinases that mediate Ca(2+)-signaling pathways [5].
• These results show that Op18 phosphorylation by CaMK IV/Gr may couple alterations of MT dynamics in response to external signals that involve Ca2+ [6].
• In addition to cell cycle-regulated phosphorylation, external signals induce phosphorylation of Op18 on Ser-25 by the mitogen-activated protein kinase and on Ser-16 by the Ca2+/calmodulin-dependent kinase IV/Gr (CaMK IV/Gr) [6].
• They also exhibit a distinct ability to undergo autophosphorylation and to phosphorylate the downstream kinases CaMK I and CaMK IV [7].

Biological context of CAMK4

• A human cDNA clone encoding CaM-kinase IV was isolated from a Jurkat cell cDNA library and its nucleotide sequence was determined [2].
• Furthermore, activation of CaM kinase IV and MAPK increased phosphorylation of CREB (cyclic AMP response element binding protein) and expression of c-Fos by stimulation of gene expression [8].
• Activated CaM-kinase IV still shows specificity for phosphorylation of Ser133, the site necessary for transactivation by CREB [9].
• CaMK IV, through activation of ERK 1/2, appears to have a direct role in the LPS signal transduction for TNFalpha production [10].

Anatomical context of CAMK4

• CaM kinase-Gr is a multifunctional Ca2+/calmodulin-dependent protein kinase which is enriched in neurons and T lymphocytes [1].
• We have isolated and sequenced cDNAs encoding Ca2+/calmodulin-dependent protein kinase type Gr (CaM-K-Gr, also called CaM-K-IV) from human brain and thymus [11].
• Effects of magnesium sulfate administration during hypoxia on CaM Kinase IV and Protein Tyrosine Kinase Activities in the cerebral cortex of newborn piglets [3].
• In this study, we examined the expression of CaM kinase-Gr in human lymphocytes and the regulation of its catalytic activity by antigen receptor signaling [12].
• GLUT4 protein increased approximately 70% 24 h after exercise but was unchanged by overexpression of CA CaMK IV in myotubes [13].

Associations of CAMK4 with chemical compounds

• Calmodulin-dependent protein kinase IV (CaM-kinase IV) phosphorylated calmodulin (CaM), which is its own activator, in a poly-L-Lys [poly(Lys)]-dependent manner [14].
• The optimum concentration of poly(Lys) for the phosphorylation of 1 microM CaM was about 10 microg/ml, but poly(Lys) strongly inhibited CaM-kinase IV activity toward syntide-2 at this concentration, suggesting that the phosphorylation of CaM is not due to simple activation of the catalytic activity [14].
• The recombinant mutant CaM-kinase IV in which Thr196 or Thr200 was replaced with nonphosphorylatable alanine showed little activity in the presence and absence of the kinase kinase [15].
• Synaptic activity, acting via the nuclear Ca(2+)-dependent activation of CaM kinase IV, triggers the disruption of subnuclear domains containing class II histone deacetylases (HDACs) and silencing mediator of retinoic acid and thyroid hormone receptors (SMRT), a broad-specificity co-repressor which represses nuclear hormone receptors and CBF1 [16].
• The CaM kinase-Gr is only expressed in certain lymphoid cell lines, and the present study shows that ionomycin-induced phosphorylation of Op18 Ser16 is restricted to cells expressing this protein kinase [17].

Enzymatic interactions of CAMK4

• CaM-K Ialpha and CaM-K IV failed to phosphorylate nNOS at Ser(847) in transfected cells [18].

Regulatory relationships of CAMK4

• CaM-kinase IV that was expressed in cancerous hepatocytes was phosphorylated mainly by CaM-kinase kinase that also was expressed in tumor cells [19].

Other interactions of CAMK4

• CaMK IV, on the other hand, is not specific for priming by PAF and appears to have a direct link in TLR4-mediated events [20].
• It was found that purified recombinant nNOS was phosphorylated by CaM-K Ialpha, CaM-K IIalpha, and CaM-K IV at Ser847 in vitro [21].
• It is likely that the lower efficiency of transcriptional activation by transfected CaM-kinase IV in previous studies was due to the fact that the CaM-kinase IV was not activated by CaM-kinase IV kinase [9].
• To determine if CaMK signaling mediates MEF2A/DNA associations in vivo, we performed ChIP assays on C(2)C(12) myotubes expressing constitutively active (CA) or dominant negative (DN) CaMK IV proteins [13].
• Nuclear Ca2+ and CaM kinase IV specify hormonal- and Notch-responsiveness [16].

Analytical, diagnostic and therapeutic context of CAMK4

• One immunoreactive band with a molecular weight of 64 kilodaltons, which was identical to an isoform of rat cerebellum CaM-kinase IV, was demonstrated by immunoblotting [19].

References