Calcium/calmodulin dependent kinase

Churn, S. B., Rana, A., Lee, K. el al. (2002). Calcium/calmodulin-dependent kinase II phosphorylation of the GABAa receptor alphal subunit modulates benzodiazepine binding. J. Neurochem. 82, 1065-76. 

A few enzymes, such as the previously mentioned CNP, are believed to be fairly specific for myelin/oligodendro-cytes. There is much more in the CNS than in peripheral nerve, suggesting some function more specialized to the CNS. In addition, a unique pH 7.2 cholesterol ester hydrolase is also enriched in myelin. On the other hand, there are many enzymes that are not myelin-specific but appear to be intrinsic to myelin and not contaminants. These include cAMP-stimulated kinase, calcium/calmodulin-dependent kinase, protein kinase C, a neutral protease activity and phosphoprotein phosphatases. The protein kinase C and phosphatase activities are presumed to be responsible for the rapid turnover of MBP phosphate groups, and the PLP acylation enzyme activity is also intrinsic to myelin. 

In the nervous system, so far there is evidence of sumoylation of at least one protein critical for synaptic plasticity. Long found that Drosophila calcium-calmodulin-dependent kinase II (CaMKII) is conjugated... 

Baudier, J. Cole, R.D. Phosphorylation of r proteins to a state like that in Alzheimers brain is catalyzed by a calcium/calmodulin-dependent kinase and modulated by phospholipids. J. Biol. Chem., 262, 17577-17583 (1987)... 

Howe, C. J., FaHair, M. M., Maxwell, J. A., Lee, J. T., Robinson, P. J., Rodriguez-Mora, O., McCubrey, J. A. and Franklin, R. A., 2002, Participation of the calcium/calmodulin-dependent kinases in hydrogen peroxide-induced Ikappa B phosphorylation in human T lymphocytes, J Biol Chem, 277, pp 30469-76. 

One of the ways in which integration to yield a monotonic response is achieved is through the initial calcium transient..As already discussed, the transient rise in intracellular calcium is responsible for stimulating calcium-calmodulin dependent kinases to bring about the initiation of the response. However, the magnitude of the sustained phase of the response also correlates with the magnitude of the initial calcium transient. Several lines of evidence indicate that this correlation reflects an effect of calcium on PKC activation. It has been demonstrated in studies with isolated red blood cell membranes that the amount of PKC which becomes associated... 

Xie et al. found that activation of the calcium/calmodulin-dependent kinase II family member (CaMKII) following NMDAR activation directly phosphory-lates kalirin-7 on its N-terminus, thereby stimulating its GEF activity (Xie et al.,... 

Fong DK, Rao A, Crump FT, Craig AM. 2002. Rapid synaptic remodeling by protein kinase C reciprocal translocation of NMDA receptors and calcium/calmodulin-dependent kinase II. J. Neurosci. 22 2153-64... 

In brain, a large number of particulate soluble proteins are phosphory-lated in the presence of Mg " -ATP and Ca +—calmodulin. These phosphorylations can be blocked by phenothiazines and do not occur in the presence of cAMP or cGMP. Furthermore, they are unaltered by the Walsh inhibitor, which is specific for the cAMP catalytic subunit. Hence, investigators have concluded that there is present in both particulate and soluble fractions of brain a Ca " -calmodulin-dependent protein kinase that is insensitive to cyclic nucleotides and that contains its own set of protein substrates. A few reports have appeared in the literature claiming purification of a calcium-calmodulin-dependent kinase from mammalian brain. The en-... 

Exposure of PC12 cells to 500 pM peroxynitrite activated extracellular-regulated kinases 1 and 2 and p38 within 5 min and this was followed by gradual decreases in activation over the next 25 min (JoPE etal. 2000). Activation of extracellular-regulated kinases 1 and 2 by peroxynitrite was mediated by activation of the epidermal growth factor receptor in a calcium/calmodulin-dependent kinase II- and sre family tyrosine kinase-dependent manner, as it was blocked by the selective epidermal growth factor receptor inhibitor AG1478, by... 

KN62, an inhibitor of calcium/calmodulin-depend-ent kinase II, and by PPl, a sre family tyrosine kinase inhibitor. Activation of p38 by peroxynitrite was independent of the epidermal growth factor receptor, required activation of calcium/calmodulin-dependent kinase II and sre family tyrosine kinases, and was modulated by nerve growth factor in a time-dependent maimer. 

In addition, vinpocetine selectively inhibits a specific calcium, calmodulin-dependent cycHc nucleotide phosphodiesterase (PDF) isozyme (16). As a result of this inhibition, cycHc guanosine 5 -monophosphate (GMP) levels increase. Relaxation of smooth muscle seems to be dependent on the activation of cychc GMP-dependent protein kinase (17), thus this property may account for the vasodilator activity of vinpocetine. A review of the pharmacology of vinpocetine is available (18). 

Akiyama, K., Suemaru, J. Effect of acute and chronic administration of methamphetamine on calcium-calmodulin dependent protein kinase II activity in the rat brain. Ann. N.Y. Acad. Sci. 914 263, 2000. 

FIGURE 1 2-2 Schematic diagram of the phosphorylation sites on each of the four 60kDa subunits of tyrosine hydroxylase (TOHase). Serine residues at the N-terminus of each of the four subunits of TOHase can be phosphorylated by at least five protein kinases. (J), Calcium/calmodulin-dependent protein kinase II (CaM KII) phosphorylates serine residue 19 and to a lesser extent serine 40. (2), cAMP-dependent protein kinase (PKA) phosphorylates serine residue 40. (3), Calcium/phosphatidylserine-activated protein kinase (PKC) phosphorylates serine 40. (4), Extracellular receptor-activated protein kinase (ERK) phosphorylates serine 31. (5), A cdc-like protein kinase phosphorylates serine 8. Phosphorylation on either serine 19 or 40 increases the activity of TOHase. Serine 19 phosphorylation requires the presence of an activator protein , also known as 14-3-3 protein, for the expression of increased activity. Phosphorylation of serines 8 and 31 has little effect on catalytic activity. The model shown includes the activation of ERK by an ERK kinase. The ERK kinase is activated by phosphorylation by PKC. (With permission from reference [72].)... 

Protein kinase Cd, Akt kinase, calcium/calmodulin-dependent protein kinase IV, mitogen-activated protein kinase kinase (MEKK-1), focal adhesion kinase (FAK), protein phosphatase (PP)2A, calcineurin... 

Koch, T., Kroslak, T., Mayer, P., Raulf, E., and HoUt, V. (1997) Site mutation in the rat mu-opioid receptor demonstrates the involvement of calcium/calmodulin-dependent protein kinase II in agonist-mediated desensitization. J. Neurochem. 69, 1767-1770. 

This enzyme [EC 2.7.1.123], also referred to as calcium/ calmodulin-dependent protein kinase type II, and micro-tubule-associated protein MAP2 kinase, catalyzes the reaction of ATP with a protein to produce ADP and an 0-phosphoprotein. The enzyme requires calcium ions and calmodulin. Proteins that can serve as substrates include vimentin, synapsin, glycogen synthase, the myosin light-chains, and the microtubule-associated tau protein. This enzyme is distinct from myosin light-chain kinase [EC 2.7.1.117], caldesmon kinase [EC 2.7.1.120], and tau-protein kinase [EC 2.7.1.135]. 

CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE Calcium carbonate (CaCOs), BIOMINERALIZATION SOLUBILITY PRODUCT Calcium hydroxide (Ca(OH)2),... 

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