Regulator, calcium dependent

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. 

Barclay J.W., Morgan A., and Burgoyne R.D. 2005 Calcium-dependent regulation of exocytosis. Cell Calcium 38, 343—353. 

Reiss, M., Lipsey, L.R., and Zhou, Z.L., Extracellular calcium-dependent regulation of transmembrane calcium fluxes in murine keratinocytes, J. Cell. Physiol. 147, 281-291, 1992. 

Association of eNOS with HSP90 has also been implicated in the regulation of NO production in a calcium-independent manner as well as in a calcium-dependent regulation. Estrogen stimulates NO production without an increase in intracellular calcium in endothelial cells. Russell et al. (2000) reported that estradiol increases NO production in human umbilical vein endothelial cells by enhancing the association of HSP90 and eNOS (Figure 2) [37]. 

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. 

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. 

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. 

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. 

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