Abstract
Calciuin (Ca2+) is involved in several types of neurofunctions, including biosynthesis of neurotransinitters (Patrick and Barchas, 1974; Morgenroth et al., 1975; Yainauchi et al., 1981), stimulus-secretion coupling of neurotransinitters and horinones (Katz and Miledi, 1967; Douglas, 1968; Rubin, 1970), inicrotubule asseinbly– disasseinbly (Weisenberg, 1972), and inany inetabolic reactions. Although the precise inolecular inechanisin inediating the actions of Ca2+ in the brain reinains to be elucidated, accuinulating evidence suggests that inany of the Ca2+ effects are inediated through calinodulin, a ubiquitous calciuin–binding protein (Cheung, 1980; Klee et al., 1980; Means and Dedinan, 1980). The protein was first discovered as a cyclic nucleotide phosphodiesterase activator (Cheung, 1970; Kakiuchi et al., 1970). Since then, inore than 10 enzyines have been reported to be regulated by calinodulin in the presence of Ca2+. Furtherinore, the action of calinodulin is regulated by calinodulin–binding proteins (Kakiuchi, 1983).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adelstein R. S. and Klee C. B. (1981) Purrfication and characterization of sinooth inuscle inyosin light chain kinase. J. Biol Chem. 256, 7501–7509.
Ahinad Z., DePaoli-Roach A. A., and Roach P. J. (1982) Purification and characterization of a rabbit liver calinodulin-dependent protein kinase able to phosphorylate glycogen synthase J. Biol. Chem. 257, 8343–8355.
Bennett M. K., Erondu N. E, and Kennedy M. B. (1983) Purification and characterization of a calinodulin-dependent protein kinase that is highly concentrated in brain J. Biol Chem. 258, 12735–12744.
Burke B E. and DeLorenzo R. J. (1981) Ca2+-and calinodulin-stiinulated endogenous phosphorylation of neurotublin. Proc Natl. Acad. Sci. USA 78, 991–995.
Burke B. E. and DeLorenzo R. J (1982a) Ca2+-and calinodulin-dependent phosphorylation of endogenous synaptic vesicle tubulin by a vesicle-bound calinodulin kinase systein. J. Neurochem. 38, 1205–1218.
Burke B. E. and DeLorenzo R J (1982b) Ca2+-and calinodulin-regulated endogenous tubulin kinase activity in presynaptic nerve terininal preparations. Brain Res. 236, 393–415.
Calmici M., Ahinad Z., DePaoli-Roach A. A, and Roach P. J (1984) Phosphorylation of rabbit liver glycogen synthase by inultiple protein kinases. J. Biol. Chem. 259, 2446–2473.
Cheung W. Y. (1970) Cyclic 3′,5′-nucleotide phosphodiesterase. Deinonstration of an activator. Biochein. Biophys. Res. Coininun. 38, 533–538.
Cheung W. Y. (1980) Calinodulin plays a pivotal role in cellular regulation. Science 207, 19–27.
Cohen P. (1982) The role of protein phosphorylation in neural and hormonal control of cellular activity. Nature 296, 613–620.
Czosnek H., Solfer D., Mack K., and Wisniewski H M. (1981) Slmilarity of neurofilament proteins froin different parts of the rabbit nervous system. Brain Res. 216, 387–398.
DeLorenzo R. J., Freedman S. D., Yohe W. B., and Maurer S. C. (1979) Stimulation of Ca2+-dependent neurotransmitter release and presynaptic nerve terminal protein phosphorylation by calmodulin and a calmodulin-like protein isolated from synaptic vesicles. Proc. Natl. Acad. Sci. USA 76, 1838–1842.
Douglas W. W. (1968) Stimulus-secretion coupling: The concept and clues from chromaffin and other cells. Brit J. Pharmacol. 34, 451–474.
Fukunaga K., Yainainoto H., Iwasa Y., and Miyainoto E. (1982a) Multiple specificities of brain Ca2+-and calmodulin-dependent protein kinase for substrate. Life Sci. 30, 2019–2024.
Fukunaga K., Yamamoto H., Matsui K., Higashi K., and Miyainoto E. (1982b) Purification and characterization of a Ca2+-and calmodulin-dependent protein kinase froin rat brain.J. Neurochem. 39,1607–1617.
Fukunaga K., Yamamoto H., Tanaka E., and Miyamoto E. (1984) A Ca-calmodulin-dependent protein kinase in the particulate fraction of rat brain and endogenous phosphorylation of particulate-bound substrates. Biomed. Res. 5, 165–176.
Goldenring J. R., Gonzalez B., McGuire J. S., Jr., and DeLorenzo R. J. (1983) Purification and characterization of a calmodulin-dependent kinase froin rat brain cytosol able to phosphorylate tubulin and microtubule-associated proteins. J. Biol. Chem. 258, 12632–12640.
Goldenring J. R., McGuire J. S., Jr., and DeLorenzo R. J, (1984) Identification of the major postsynaptic density protein as homologous with the major calinodulin-binding subunit of a calinodulin-dependent protein kinase. J. Neurochem. 42, 1077–1084.
Gorelick F. S., Cohn J. A, Freedman S. D., Delahunt N. G., Gershoni J. M., and Jamieson J. D. (1983) Calmodulin-stimulated protein kinase activity from rat pancreas J Cell Biol 97, 1294–1298.
Grab D. J., Carlin R. K., and Siekevitz P. (1981) Function of calmodulin in postsynaptic densities. II Presence of a calmodulin-activatable protein kinase activity. J. Cell Biol. 89, 440–448.
Greengard P (1978) Cyclic Nucleotides, Phosphorylated Proteins, and Neuronal Function. Raven, New York.
Greengard P. (1983) Neuron-specific phosphoproteins in mammalian brain. Proc. 5th Int. Conf Cyclic Nucleotides and Protein Phosphorylation, p. 92.
Hatada Y., Munemura M., Fukunaga K., Yamamoto H., Maeyama M., and Miyamoto E. (1983) Calmodulin and Ca2+-and calmodulin-dependent protein kinase in rat anterior pituitary gland J Neurochem. 40, 1082–1089.
Hathaway D R. and Adelstein R. S. (1979) Human platelet myosin light chain kinase requires the calcium binding protein, calmodulin, for activity. Proc. Nat1 Acad Sci USA 76, 1653–1657.
Hathaway D. R., Adelstein R S, and Klee C. B. (1981) Interaction of calmodulin with myosin light chain kinase and cAMP-dependent protein kinase in bovine brain. J. Biol. Chem. 256, 8183–8189.
Higashi K., Fukunaga K, Matsui K, Maeyama M., and Miyamoto E (1983) Purification and characterization of myosin light-chain kinase from porcine myometrium and its phosphorylation and modulation by cyclic AMP-dependent protein kinase. Biochim. Biophys Acta 747, 232–240.
Huttner W. B., DeGennaro L J, and Greengard P. (1981) Differential phosphorylation of multiple sites in purified protein I by cychc AMP-dependent and calmodulin-dependent protein kinases. J. Biol Chem 256, 1482–1488.
Iinazu M., Strickland W G, Chrisman T. D., and Exton J H (1984) Phosphorylation and mactivation of liver glycogen synthase by liver protein kinases. J Biol Chem 259, 1813–1821.
Ishizaki Y, Tashiro T, and Kurokawa M (1983) A calcium-activated protease which preferentially degrades the 160,000-kDa component of the neurofilament triplet Eur J Biochem. 131, 41–45.
Iwasa T., Fukunaga K, Yamamoto H., Tanaka E, and Miyamoto E. (1983) Ca2+, calmodulin-dependent phosphorylation of glycogen synthase by a brain protein kinase. FEBS Lett 161, 28–32.
Iwasa T, Fukunaga K, Yamamoto H, Tanaka E., and Miyamoto E (1984) Ca2+, calmodulin-dependent phosphorylation, and inactivation of glycogen synthase by a brain protein kinase. Arch. Biochem Biophys.. 235, 212–217.
Jameson L. and Caplow M (1981) Modification of microtubule steadystate dynamics by phosphorylation of the microtubule-associated proteins. Proc. Nat1 Acad Sci USA 78, 3413–3417.
Julien J.-P. and Mushynski W. E. (1981) A comparison of in vitro-and in vivo-phosphorylated neurofilament polypeptides. J Neurochem 37, 1579–1585.
Juhen J-P, Smoluk G. D, and Mushynski W. E. (1983) Characteristics of the protein kinase activity associated with rat neurofilament preparations. Biochim Biophys. Acta 755, 25–31.
Kakiuchi S. (1983) Calmodulin-binding proteins in brain. Neurochem Int. 5, 159–169.
Kakiuchi S., Yamazaki R, and Nakajima H. (1970) Properties of a heat-stable phosphodiesterase activity factor Isolated from brain extract. Proc Jpn Acad 46, 587–592.
Katz B. and Miledi R. (1967) A study of synaptic transmission in the absence of nerve impulses. J Physio. (Lond.) 192, 407–436.
Kelly P. T., McGuinness T L., and Greengard P (1984) Evidence that the major postsynaptic density protein is a component of a Ca2+/calmodulm-dependent protein kinase. Proc Natl. Acad. Sci. USA 81, 945–949.
Kennedy M. B and Greengard P (1981) Two calcium/calmodulin-dependent protein kinases, which are highly concentrated in brain, phosphorylate protein I at distinct sites. Proc. Natl. Acad. Sci USA 78, 1293–1297.
Kennedy M. B., McGuinness T., and Greengard P. (1983) A calcium/calmodulin-dependent protein kinase from mammalian brain that phosphorylates synapsin. I. Partial purification and characterization. J Neurosci 3, 818–831.
Klee C B., Crouch T H.,and Richman P G. (1980) Calmodulin Ann.Rev.Biochem 49, 489–515.
Krebs E.G. and Beavo J. A. (1979) Phosphorylation-dephosphorylation of enzymes. Ann Rev Biochem 48, 923–939.
Kumagai H and Nishida E. (1979) The interactions between calcium-dependent regulator protein of cyclic nucleotide phosphodiesterase and microtubule proteins II Association of calcium-dependent regulator protein with tubulin dimer. J. Biochem. 85, 1267–1274.
Kuret J. and Schulman H (1984) Purification and characterization of a Ca2+/calmodulin-dependent protein kinase from rat brain. Biochemistry 23, 5495–5504.
Laemmli U. K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685.
Lazarides E. (1982) Intermediate filaments: A chemicaIly heterogenous, developmentally regulated class of proteins. Ann. Rev. Biochem. 51, 219–250.
Lee Y. C. and Wolff J. (1982) Two opposing effects of calmodulin on microtubule assembly depend on the presence of microtubule-associated proteins. J. Biol Chem. 257, 6306–6310.
Lee Y C and Wolff J. (1984) Calmodulin binds to both microtubule-associated protein 2 and 7 proteins. J. Biol Chem. 259, 1226–1230.
Leterner J.-F., Liem R. K. H, and Shelanski M L. (1981) Preferential phosphorylation of the 150,000 molecular weight component of neurofilaments by a cyclic AMP-dependent, microtubule-associated protein kinase. J. Cell Biol. 90, 755–760.
Levin R. M and Weiss B (1979) Selective binding of antipsychotics and other psychoactive agents to the calcium-dependent activator of cyclic nucleotide phosphodiesterase. J. Pharmacol. Exp Ther. 208, 454–459.
Marcuin J. M, Dedman J R., Brinkley B. R., and Means A. R. (1978) Control of microtubule assembly-disassembly by calcium-dependent regulator protein. Proc. Natl Acad. Sci USA 75, 3771–3775.
Matsuda G., Suzuyama Y., Maita T., and Umegane T. (1977) The L-2 light chain of chicken skeletal muscle myosin. FEBS Lett. 84, 53–56.
McGuiness T L., Lai Y, Greengard P., Woodgett J R., and Cohen P (1983) A multifunctional calmodulin-dependent protein kinase. Similarities between skeletal muscle glycogen synthase kinase and a brain synapsin I kinase. FEBS Lett. 163, 329–334.
Means A R. and Dedman J. R (1980) Calmodulin—an intracellular calcium receptor. Nature 285, 73–77.
Miyamoto E., Fukunaga K., and Matsui K. (1982) Demonstration of Two Types of Ca2+ Dependent Protein Kinases in the Brain and Other Tissues, in Calmodulin and Intracellular Ca 2+ Receptors (Kakiuchi S., Hidaka H., and Means A. R., eds.), pp. 255–265, Plenum, New York.
Miyamoto E., Fukunaga K., Matsui K., and Iwasa Y. (1981a) Occurrence of two types of Ca2+-dependent protein kinases in the cytosol fraction of the brain. J Neurochem. 37, 1324–1330.
Miyamoto E., Matsui K., Fukunaga K., Nishime S., and Iwasa Y. (1981b) The occurrence of myosin light chain kinase in non-muscle tissues Biomedical Res. 2, 341–346.
Miyamoto E., Miyazaki K, Hirose R, and Kashiba A. (1978) Multiple forms of protein kinases in myelin and microsomal fractions of bovine brain. J. Neurochem. 31, 269–275.
Miyamoto E., Petzold G. L, Kuo J. F., and Greengard P. (1973) Dissociation and activation of adenosme 3′,5′-monophosphate-dependent and guanosme 3′,5′-monophosphate-dependent protein kinase by cyclic nucleotides and by substrates.. 248, 179–189.
Morgenroth V. H., Boadle-Biber M. C., and Roth R. H. (1975) Activation of tyrosine hydroxylase from central noradrenergic neurons by calcium. Mol. Pharmacol. 11, 427–435.
Moskowitz N., Glassman A., Ores C., Schook W., and Puszkin S. (1983) Phosphorylation of brain synaptic and coated vesicle proteins by endogenous Ca2+/calmodulin-and cAMP-dependent protein kinases. J. Neurochem 40, 711–718.
Nimmo H G., Proud C. G, and Cohen P. (1976) The purification and properties of rabbit skeletal muscle glycogen synthase. Eur J.Biochem. 68, 21–30.
Nishida E, Kumagai H., Ohtsuki I, and Sakai H. (1979) The interactions between calcium-dependent regulator protein of cyclic nucleotide phosphodiesterase and microtubule proteins. I Effect of calcium-dependent regulator protein on the calcium sensitivity of microtubule assembly J Biochem. 85, 1257–1266.
Nonomura Y. and Ebashi S. (1975) Isolation and Identificatron of Smooth Muscle Contractile Proteins, in Methods in Pharmacology, Vol. 3: Smooth Muscle (Daniel E. E. and Paton D M., eds.), pp. 141–162, Plenum, New York.
O’Callaghan J. P., Dunn L. A, and Lovenberg W (1980) Calcium-regulated phosphorylation in synaptosomal cytosol: Dependence on calmodulin Proc. Natl. Acad. Sci. USA 77, 5812–5816.
Palfrey H. C., Rothlein J. E., and Greengard P. (1983) Calmodulin-dependent protein kinase and associated substrates in Torpedo electric organ J Biol. Chem. 258, 9496–9505.
Patrick R L. and Barchas J. D. (1974) Stimulation of synaptosomal dopamme synthesis by veratridine. Nature 250, 737–739.
Payne M. E, Schworer C. M., and Soderling T. R. (1983) Purification and characterization of rabbit liver calmodulin-dependent glycogen synthase kinase. J. Biol Chem. 258, 2376–2382.
Payne M. E. and Soderling T R. (1980) Calmodulin-dependent glycogen synthase kinase. J. Biol. Chem 255, 8054–8056.
Perrie W T. and Perry S V (1970) An electrophoretic study of the low-molecular weight components of myosin. Biochem. J. 119,31–38.
Pires E M V and Perry S. V. (1977) Purification and properties of myosin light chain kinase from fast skeletal muscle. Biochem. J 167, 137–146.
Roach P. J. (1981) Glycogen synthase and glycogen synthase kinases Curr, Top. Cell. Reg. 20, 45–105.
Rubin R. P. (1970) The role of calcium in the release of neurotransmitter substances and hormones. Pharmacol. Rev. 22, 389–428.
Schulman H. and Greengard P. (1978a) Stimulation of brain membrane protein phosphorylation by calcium and an endogenous heat-stable protein. Nature 271, 478–479.
Schulman H and Greengard P. (1978b) Ca2+-dependent protein phosphorylation system in membranes from various tissues, and its activation by “calcium-dependent regulator.” Proc. Natl. Acad. Sci USA 75, 5432–5436.
Schworer C M and Soderling T. R (1983) Substrate specificity of liver calmodulin-dependent glycogen synthase kinase Biochem Biophys Res. Commun. 116, 412–416
Shelanski M. L, Gaskin F, and Cantor C. R. (1973) Microtubule assembly in the absence of added nucleotides Proc Natl. Acad. Sci USA 70, 765–768.
Sieghart W., Forn J., and Greengard P (1979) Ca2+ and cyclic AMP regulate phosphorylation of same two membrane-associated proteins specific to nerve tissue Proc Natl Acad Sci USA 76, 2475–2479.
Sobue K., Fujita M, Muramoto Y., and Kakiuchi S (1981) The calmodulin-binding protein in microtubules is tau factor FEBS Lett. 132, 137–140.
Sobue K., Kanda K., and Kakiuchi S (1982) Solubilization and partial purification of protein kinase systems from brain membranes that phosphorylate calspectin. A spectrin-like calmodulin-binding protein (fodrin). FEBS Lett 150, 185–190.
Sorensen R G. and Mahler H. R. (1983) Calcium-stimulated protein phosphorylation in synaptic membranes. J. Neurochem. 40, 1349–1365.
Takeda Y, Brewer H B, and Larner J. (1975) Structural studies on rabbit muscle glycogen synthase. I. Subunit composition. J. Biol. Chem. 250, 8943–8950.
Tanaka E., Miyamoto E, Tashiro T., Komiya Y., and Kurokawa M. (1984) Ca2+-calmodulin-dependent and cyclic AMP-dependent phosphorylation of neurofilaments and glial fibrillary acidic protein. Biomedical Res., 5, 239–244.
Walaas S. I., Nairn A C., and Greengard P. (1983) Regional distribution of calcium-and cyclic adenosine 3′:5′-monophosphate-regulated protein phosphorylation systems in mammalian brain, I. Particulate systems. J. Neurosci. 3, 291–301.
Walsh M P, Vallet B, Autric F., and Demaille J. G. (1979) Purification and characterization of bovine cardiac calmodulin-dependent myosin light chain kinase J. Biol Chem. 254, 12136–12144.
Weisenberg R C. (1972) Microtubule formation in vitro in solutions containing low calcium concentrations. Science 177, 1104–1105.
Woodgett J R., Davison M. T., and Cohen P. (1983) The calmodulin-dependent glycogen synthase kinase from rabbit skeletal muscle Purification, subunit structure and substrate specificity. Eur. J. Biochem 136, 481–487.
Woodgett J. R., Tonks, N K., and Cohen P. (1982) Identification of a calmodulin-dependent glycogen synthase kinase in rabbit skeletal muscle, distinct from phosphorylase kinase. FEBS Lett. 148, 5–11.
Wrenn R W., Katoh N, Wise B. C., and Kuo J. F. (1980) Stimulation by phosphatidylserine and calmodulin of calcium-dependent phosphorylation of endogenous proteins from cerebral cortex. J. Biol.Chem. 255, 12042-12046.
Yamamoto H., Fukunaga K, Goto S, Tanaka E., and Miyamoto E (1985) Ca2+, calmodulin-dependent regulation of microtubule formation via phosphorylation of microtubule-associated protein 2, Υ factor, and tubulin, and comparison with the cyclic AMP-dependent phosphorylation J Neurochem. 44, 759–768.
Yamamoto H., Fukunaga K, Tanaka E., and Miyamoto E. (1983) Ca2+-and calmodulin-dependent phosphorylation of microtubule-associated protein 2 and Υ factor, and inhibition of microtubule assembly J. Neurochem. 41, 1119–1125.
Yamauchi T. and Fulisawa H (1979a) Activation of tryptophan 5-monooxygenase by calcium-dependent regulator protein. Biochem.Biophys Res. Commun. 90, 28–35.
Yamauchi T. and Fujisawa H. (1979b) Most of the Ca2+-dependent endogenous phosphorylation of rat brain cytosol proteins requires Ca2+-dependent regulator protein. Biochem. Biophys Res. Commun 90, 1172–1178.
Yamauchi T. and Fujisawa H. (1980) Evidence for three distinct forms of calmodulin-dependent protein kinases from rat brain. FEBS Lett. 116, 141–144.
Yamauchi T. and Fujisawa H. (1982) Phosphorylation of microtubule-associated protein 2 by calmodulin-dependent protein kinase (kinase II) which occurs only in the brain tissues. Biochem. Biophys Res. Commun. 109, 975–981.
Yamauchi T and Fujisawa H (1983a) Disassembly of microtubules by the action of calmodulin-dependent protein kinase (kinase II) which occurs only in the brain trssues. Biochem. Biophys. Res. Commun. 110, 287–291.
Yamauchi T. and Fulisawa H. (1983b) Purification and characterization of the brain calmodulin-dependent protein kinase (kinase II), which is involved in the activation of tryptophan 5-monooxygenase. Eur J Biochem 132, 15–21.
Yamauchi T., Nakata H, and Fulisawa H. (1981) A new activator protein that activates tryptophan 5-monooxygenase and tyrosine 3-monooxygenase in the presence of Ca2+-, calmodulin-dependent protein kinase. Purification and characterization. J. Biol. Chem. 256, 5404–5409.
Yazawa M., Sakuma M., and Yagi K. (1980) Calmodulins from muscles of marine invertebrates, scallop and sea anemone. Comparison with calmodulins from rabbit skeletal muscle and pig brain. J Biochem. 87,1313–1320.
Author information
Authors and Affiliations
Editor information
Rights and permissions
Copyright information
© 1986 The Humana Press Inc.
About this protocol
Cite this protocol
Miyamoto, E. (1986). Characterization of a Multifunctional Ca2+-Calmodulin-Dependent Protein Kinase in the Brain. In: Boulton, A.A., Baker, G.B., Yu, P.H. (eds) Neurotransmitter Enzymes. Neuromethods, vol 5. Humana Press. https://doi.org/10.1385/0-89603-079-2:519
Download citation
DOI: https://doi.org/10.1385/0-89603-079-2:519
Publisher Name: Humana Press
Print ISBN: 978-0-89603-079-4
Online ISBN: 978-1-59259-610-2
eBook Packages: Springer Protocols