Calcium/calmodulin-dependent

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). 

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. 

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. 

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. 

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... 

Kahl CR, Means AR (2003) Regulation of cell cycle progression by calcium/calmodulin-dependent pathways. Endocr Rev 24 719-736... 

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... 

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),... 

Yang Y, Cheng P, Zhi G, Liu Y 2001 Identification of a calcium/calmodulin-dependent protein kinase that phosphorylates the Neurospora clock protein FREQUENCY. J Biol Chem 276 41064-41072... 

Wolfman C, Fin C, Dias M, Bianchin M, Da Silva RC, Schmitz PK, Medina JH, Izquierdo 1 (1994) Intrahippocampal or intraamygdala infusion of KN62, a specific inhibitor of calcium/calmodulin-dependent protein kinase 11, causes retrograde amnesia in the rat. Behav Neural Biol 61 203-205... 

Before discussing some of the observations concerning -NO in our laboratory, it is important to review a few of the basic principles of "NO production and mechanism of action. More detail on these topics can be found in other chapters in this book. First, "NO production can occur by one of two categories of NOS enzymes. Constitutive enzymes are expressed in various cell types, including endothelial cells, neurons, and neutrophils. Production of "NO by this type of enzyme is typically calcium/calmodulin-dependent and occurs immediately. This type of production has also been referred to as low output. Cells such as macrophages, hepatocytes, and smooth muscle cells express an inducible NO synthase. The induction of this enzyme typically results from exposure of the cells... 

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)... 

Communi, D. Dewaste, V. Erneux, C. Calcium-calmodulin-dependent protein kinase II and protein kinase C-mediated phosphorylation and activation of D-myo-inositol 1,4, 5-trisphosphate 3-kinase B in astrocytes. J. Biol. Chem., 274, 14734-14742 (1999)... 

Activity is modulated by other proteins present in the membrane. These include a glycoprotein (MW 53 000) which stimulates ATPase activity 138 a 60 000 molecular weight protein, which is phosphorylated in a calmodulin-dependent fashion, affects accumulation of calcium 139 while the activity of the enzyme is affected by an endogenous kinase and phosphatase which phosphorylates and dephosphorylates the protein.140 Phospholamban is a proteolipid (MW 22 000) in cardiac SR which undergoes both cyclic AMP-dependent and calcium-calmodulin-dependent phosphorylation,141 but at different sites. All these proteins are probably involved in regulating the activity of the calcium pump. 

Enslen H., Tokumitsu H., Stork R J., Davis R. J., and Soderling T. R. (1996). Regulation of mitogen-activated protein kinases by a calcium/calmodulin-dependent protein kinase cascade. Proc. Natl. Acad. Sci. USA 93 10803-10808. 

Moriguchi S., Han F., Nakagawasai O., Tadano T., and Fukunaga K. (2006). Decreased calcium/calmodulin-dependent protein kinase II and protein kinase C activities mediate impairment of hippocampal long-term potentiation in the olfactory bulbectomized mice. J. Neurochem. 97 22-29. 

Chow, F. A., Anderson, K. A., Noeldner, P. K. and Means, A. R., 2005, The autonomous activity of calcium/calmodulin-dependent protein kinase IV is required for its role in transcription, J Biol Chem, 280, pp 20530-8. 

Chow, F. A. and Means, A. R., 2006, The Calcium/Calmodulin-Dependent Protein Kinase Cascades, New Comprehensive Biochemistry-Calcium, A Matter of Life or Death, (J. Krebs and M. Michalak), Elsevier B.V. 

Haribabu, B., Hook, S. S., Seibert, M. A., Goldstein, E. G., Tomhave, E. D., Edelman, A. M., Snyderman, R. and Means, A. R., 1995, Human calcium-calmodulin dependent protein kinase I cDNA cloning, domain structure and activation by phosphorylation at threonine-177 by calcium-calmodulin dependent protein kinase I kinase, Embo J, 14, pp 3679—3686. 

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. 

---