Calmodulin-dependent protein kinase kinases

Keywords calmodulin dependent protein kinase, kinase cascade, cell cycle regulation, apoptosis,... 

Hawley, S. A., Pan, D. A., Mustard, K. J., Ross, L., Bain, J., Edelman, A. M., Frenguelli, B. G. and Hardie, D. G., 2005, Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase, Cell Metab, 2, pp 9-19. 

Hong, S. P., Momcilovic, M. and Carlson, M., 2005, Function of mammalian LKB1 and Ca2+/calmodulin-dependent protein kinase kinase alpha as Snfl-activating kinases in yeast, J Biol Chem, 280, pp 21804-9. 

Hsu, L. S., Chen, G. D., Lee, L. S., Chi, C. W., Cheng, J. F. and Chen, J. Y., 2001, Human Ca2+/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity, J Biol Chem, 276, pp 31113-23. 

Nakamura, Y., Okuno, S., Kitani, T., Otake, K., Sato, F. and Fujisawa, H., 2001, Immunohistochemical localization of Ca(2+)/calmodulin-dependent protein kinase kinase beta in the rat central nervous system, Neurosci Res, 39, pp 175-88. 

Sakagami, H., Umemiya, M., Saito, S. and Kondo, H., 2000, Distinct immunohistochemical localization of two isoforms of Ca2+/calmodulin-dependent protein kinase kinases in the adult rat brain, Eur J Neurosci, 12, pp 89—99. 

Tokumitsu, H., Enslen, H. and Soderling, T. R., 1995, Characterization of a Ca2+/calmodulin-dependent protein kinase cascade. Molecular cloning and expression of calcium/calmodulin-dependent protein kinase kinase, J Biol Chem, 270, pp 19320—4. 

Tokumitsu, H., Takahashi, N., Eto, K., Yano, S., Soderling, T. R. and Muramatsu, M., 1999, Substrate recognition by Ca2+/Calmodulin-dependent protein kinase kinase. Role of the arg-pro-rich insert domain, J Biol Chem, 274, pp 15803-10. 

Vinet, J., Carra, S., Blom, J. M., Harvey, M., Brunello, N., Barden, N. and Tascedda, F., 2003, Cloning of mouse Cal - -/calmodulin-dependent protein kinase kinase beta (CaMKKbeta) and characterization of CaMKKbeta and CaMKKalpha distribution in the adult mouse brain, Brain Res Mol Brain Res,... 

AMPK can also be activated by a Ca2+-mediated pathway involving phosphorylation at Thr-172 by the Ca2+/calmodulin-dependent protein kinase, CaMKK 3. CaMKKa and CaMKK 3 were discovered as the upstream kinase for the calmodulin-dependent protein kinases-1 and -IV they both activate AMPK in a Ca2+/ calmodulin-dependent manner in cell-free assays, although CaMKK 3 appears to much more active against AMPK in intact cells. Expression of CaMKKa and CaMKK(3 primarily occurs in neural tissues, but CaMKKp is also expressed in some other cell types. Thus, the Ca2+-mediated pathway for AMPK activation has now been shown to occur in response to depolarization in rat neuronal tissue, in response to thrombin (acting via a Gq-coupled receptor) in endothelial cells, and in response to activation of the T cell receptor in T cells. 

Finally, entry of Ca + through somatic and dendritic Ca + channels activates calmodulin-dependent protein kinases to modulate transcription, and thereby plays a crucial role in certain components of neural development and plasticity. 

So far, it has been established from in vitro studies that the enzyme undergoes phosphorylation, a process that changes the conformation of the enzyme protein and leads to an increase in its activity. This involves Ca +/calmodulin-dependent protein kinase II and cAMP-dependent protein kinase which suggests a role for both intracellular Ca + and enzyme phosphorylation in the activation of tryptophan hydroxylase. Indeed, enzyme purified from brain tissue innervated by rostrally projecting 5-HT neurons, that have been stimulated previously in vivo, has a higher activity than that derived from unstimulated tissue but this increase rests on the presence of Ca + in the incubation medium. Also, when incubated under conditions which are appropriate for phosphorylation, the of tryptophan hydroxylase for its co-factor and substrate is reduced whereas its Fmax is increased unless the enzyme is purified from neurons that have been stimulated in vivo, suggesting that the neuronal depolarisation in vivo has already caused phosphorylation of the enzyme. This is supported by evidence that the enzyme activation caused by neuronal depolarisation is blocked by a Ca +/calmodulin protein kinase inhibitor. However, whereas depolarisation... 

LiuD, MatzukMM, Sung WK, Guo Q, WangP, Wolgemuth DJ 1998 Cyclin A1 is required for meiosis in the male mouse. Nat Genet 20 377-380 Lorca T, Cruzalequi FH, Fesquet D et al 1993 Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF activities upon fertilization of Xenopus eggs. Nature 366 270-273... 

Winston N J 1997 Stability of cyclin B protein during meiotic maturation and the first mitotic cell division in mouse oocytes. Biol Cell 89 211-219 Winston NJ, Maro B 1995 Calmodulin-dependent protein kinase II is activated transiently in ethanol-stimulated mouse oocytes. Dev Biol 170 350-352 Winston NJ, Bourgain-Guglielmetti F, Ciemerych MA et al 2000 Early development of mouse embryos null mutant for the cyclin A2 gene occurs in the absence of maternally derived cyclin A2 gene products. Dev Biol 223 139-153... 

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. 

Bagni, C., Mannucci, L., Dotti, C. G., and Amaldi, F. (2000). Chemical stimulation of synaptosomes modulates alpha —Ca2+/calmodulin-dependent protein kinase II mRNA association to polysomes. J. Neurosci. 20, RC76. 

Takao, K., Okamoto, K., Nakagawa, T., Neve, R. L., Nagai, T., Miyawaki, A., Hashikawa, T., Kobayashi, S. and Hayashi, Y. (2005). Visualization of synaptic Ca2+/calmodulin-dependent protein kinase II activity in living neurons. J. Neurosci. 25, 3107-12. 

The synthesis of 5-HT can increase markedly under conditions requiring more neurotransmitter. Plasticity is an important concept in neurobiology. In general, this refers to the ability of neuronal systems to conform to either short- or long-term demands placed upon their activity or function (see Plasticity in Ch. 53). One of the processes contributing to neuronal plasticity is the ability to increase the rate of neurotransmitter synthesis and release in response to increased neuronal activity. Serotonergic neurons have this capability the synthesis of 5-HT from tryptophan is increased in a frequency-dependent manner in response to electrical stimulation of serotonergic soma [7]. The increase in synthesis results from the enhanced conversion of tryptophan to 5-HTP and is dependent on extracellular calcium ion. It is likely that the increased 5-HT synthesis results in part from alterations in the kinetic properties of tryptophan hydroxylase, perhaps due to calcium-dependent phosphorylation of the enzyme by calmodulin-dependent protein kinase II or cAMP-dependent protein kinase (PKA see Ch. 23). 

Soderling, T. R. Modulation of glutamate receptors by cal-cium/calmodulin-dependent protein kinase II. Neurochem. Int. 28 359-361,1996. 

ALD adrenoleukodystrophy CaMK Ca2+-calmodulin-dependent protein kinase cyclic adenosine 3, 5 -monophosphate... 

The affect of Li+ on the metabolism of serotonin (5-hydroxytryp-tamine, 5-HT) is equivocal. A number of studies consistently find a Li+-induced increase in the levels of the major metabolite, 5-hydroxyin-doleacetic acid (5-HIAA), in rat brain and in human CSF [155], which appears to reflect an increase in the rate of synthesis of 5-HT [156]. Li+-induced increases in the level of the amino acid precursor, tryptophan, and in the uptake of tryptophan by brain have also been reported [157], implying elevated tryptophan availability during Li+ treatment. In rat brain, chronic Li+ decreases the activity of tryptophan hydroxylase, the enzyme which, when activated by a Ca2+ and calmodulin-dependent protein kinase, leads to the synthesis of 5-HT [158]. Ca2+ increases the strength of binding of tryptophan to the enzyme, whereas Li+ has the opposite effect [159]. Tryptophan uptake is coupled to 5-HT utilization by a negative feedback mechanism and, therefore, the Li+-induced inhibition of tryptophan hydroxylase with a resultant decrease in 5-HT utilization could produce the observed increase in tryptophan uptake. 

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... 

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