Calcium-dependent regulator protein

Welsh, M. J., Dedman, J. R., Brinkley, B. R., and Means, A. R., 1978, Calcium-dependent regulator protein Localization in mitotic apparatus of eukaryotic cells, Proc. Natl. Acad. Sci. USA 75 1867. 

Srivastava, A. K., Waisman, D. M., Brostrom, C. O., and Soderling, T. R., 1979, Stimulation of glycogen synthase phosphorylation by calcium-dependent regulator protein, /. Biol Chem. 254 583. 

Calcium-dependent regulation involves the calcium-calmodulin complex that activates smooth muscle MLCK, a monomer of approximately 135 kDa. Dephosphorylation is initiated by MLCP. MLCP is a complex of three proteins a 110-130 kDa myosin phosphatase targeting and regulatory subunit (MYPT1), a 37 kDa catalytic subunit (PP-1C) and a 20 kDa subunit of unknown function. In most cases, calcium-independent regulation of smooth muscle tone is achieved by inhibition of MLCP activity at constant calcium level inducing an increase in phospho-rMLC and contraction (Fig. 1). 

Palfrey, H. C. and Nairn, A. C. Calcium-dependent regulation of protein synthesis. Adv. Second Messenger Phosphoprotein Res. 30 191-223,1995. 

Loyet KM, Kowalchyk JA, Chaudhary A et al (1998) Specific binding of phosphatidylinositol 4,5-bisphosphate to calcium-dependent activator protein for secretion (CAPS), a potential phos-phoinositide effector protein for regulated exocytosis. J Biol Chem 273 8337 13 Luscher C, Jan LY, Stoffel M et al (1997) G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. Neuron 19 687-95... 

A calcium regulated enzyme or protein could be considered as the third type of calcium binding protein. The calcium regulated enzyme is contrasted to the target protein of the calcium dependent regulatory protein in that the calcium regulated enzymes are capable of binding calcium directly and do not require additional proteins to confer calcium sensitivity. An example of this type of calcium receptor is the protein kinase C [8]. 

Other possible opiate activation sites could involve certain ATPases associated with calmodulin. A growing literature suggests that such Ca2+-dependent regulator proteins (calcium dependent regulator) regulate the activity of a number of enzymes such as phosphodiesterase (93) and adenylate cyclase (94) via the formation of Ca +-CDR -enzyme complexes in response to Ca + fluxes. Thus, they appear to represent a link between different types of cell messenger, namely Ca + and cAMP. It has further been postulated that calmodulin, a CDR protein, is a likely Ca + receptor site (95). These proteins may thus represent an important site for Ca +-opiate interactions, with consequent alteration of enzyme activity. 

Calmodulin (CaM) is a ubiquitous intracellular protein that mediates more than 100 different biological systems in both calcium-free and -loaded forms. CaM has 148 amino acids and its primary sequence is highly conserved in all cell types. It shares strong sequence and structure homology to TnC, which is involved solely in the Calcium-dependent regulation of skeletal and heart muscle contraction. Yeast (yCaM) is 60% identical in sequence to vertebrate CaMs and contains only three functional sites. Several labs have shown that the prokaryotes have several CaM-like proteins containing two or more authentic EF-hand motifs. 

Calmodulin, calcium-dependent regulator, CDR, calcium modulator, CaM, a Ca +-binding protein (148 aa Mr 17 kDa) that mediates various functions in eukaryotes. It contains two similar globular domains separated by a seven-turn a-helix, and two... 

Kameyama, T. and Etlinger, J.D., Calcium-dependent regulation of protein synthesis and degradation in muscle. Nature, 279, 344, 1979. 

Brostrom, C. O., Huang, Y.-C., Breckenridge, B. McL., and Wolff, D. J., 1975, Identification of a calcium-binding protein as a calcium-dependent regulator of brain adenylate cyclase, Proc. Natl. Acad. Sci. USA 72 64. 

Schulman, H., and Greengard, P., 1978, Ca +-dependent protein phosphorylation system in membranes from various tissues, and its activation by "calcium-dependent regulator," Proc. Natl. Acad. Sci. USA 75 5432. 

In addition to intracellular heme-containing proteins, big-conductance calcium-dependent K+ (BKCa) channels and calcium-spark activated transient Kca channels in plasma membrane are also tar geted by CO [3]. As well known, nitric oxide (NO) also activates BKca channels in vascular smooth muscle cells. While both NO and CO open BKCa channels, CO mainly acts on alpha subunit of BKCa channels and NO mainly acts on beta subunit of BKca channels in vascular smooth muscle cells. Rather than a redundant machinery, CO and NO provide a coordinated regulation of BKca channel function by acting on different subunits of the same protein complex. Furthermore, pretreatment of vascular smooth muscle... 

Calmodulin, a calcium binding protein, is involved in Ca2+-dependent regulation of several synaptic functions of the brain synthesis, uptake and release of neurotransmitters, protein phosphorylation and Ca+2 transport. It reacts with TET, TMT and TBT which then inactivates enzymes like Ca+2-ATPase and phosphodiesterase. In vitro studies indicated TBT was greater at inhibiting calmodulin activity than TET and TMT, whereas in vivo the order was TET > TMT > TBT. This may be due to the greater detoxification of TBT (66%) in the liver before moving to other organs30,31. 

During the last ten years, it has become apparent that calcium-dependent papain-like peptidases called calpains (EC 3.4.22.17) represent an important intracellular nonlysosomal enzyme system [35][36], These enzymes show limited proteolytic activity at neutral pH and are present in virtually every eukaryotic cell type. They have been found to function in specific proteolytic events that alter intracellular metabolism and structure, rather than in general turnover of intracellular proteins. Calpains are composed of two nonidentical subunits, each of which contains functional calcium-binding sites. Two types of calpains, i.e., /i-calpain and m-calpain (formerly calpain I and calpain II, respectively), have been identified that differ in their Ca2+ requirement for activation. The activity of calpains is regulated by intracellular Ca2+ levels. At elevated cytoplasmic calcium concentrations, the precursor procal-pain associates with the inner surface of the cell membrane. This interaction seems to trigger autoproteolysis of procalpain, and active calpain is released into the cytoplasm [37]. 

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