Phosphorylation calcium sensitivity

The major relaxing transmitters are those that elevate the cAMP or cGMP concentration (Fig. 3). Adenosine stimulates the activity of cAMP kinase. The next step is not clear, but evidence has been accumulated that cAMP kinase decreases the calcium sensitivity of the contractile machinery. In vitro, cAMP kinase phosphorylated MLCK and decreased thereby the affinity of MLCK for calcium-calmodulin. However, this regulation does not occur in intact smooth muscle. Possible other substrate candidates for cAMP kinase are the heat stable protein HSP 20, (A heat stable protein of 20 kDa that is phosphorylated by cGMP kinase. It has been postulated that phospho-HSP 20 interferes with the interaction between actin and myosin allowing thereby smooth muscle relaxation without dephosphorylation of the rMLC.) Rho A and MLCP that are phosphorylated also by cGMP kinase I (Fig. 3). 

In the budding yeast, inositol polyphosphate synthesis proceeds via what is likely to be one of the earliest incarnations of a PLC-dependent pathway for higher inositol polyphosphate metabolism in eukaryotes. Early biochemical studies in yeast (and plants) failed to identify a calcium-sensitive Ins(l,4,5)P3 3-kinase activity analogous to that found in mammalian cells. Instead, these studies identified C6-hydroxyl phosphorylation of Ins(l,4,5)P3 and formation of Ins(l,4,5,6)P4 as the most likely first anabolic step in the production of higher inositol polyphosphates (22). Additional biochemical studies identified the sequential phosphorylation of Ins(l,4,5,6)P4 to Ins(l,3,4,5,6)P5 followed by Ins(l,2,3,4,5,6)P6 (23). These findings were interpreted as proof of the existence of disparate pathways in yeast and mammals for the metabolism and functionality of Ins(l,4,5)P3. In contrast, the eventual cloning of the yeast Ins(l,4,5)P3 kinase activity found that mammalian and yeast inositol metabolism were more closely related than initially suspected. 

K-Casein is the only eutherian casein that has conclusively been shown to contain carbohydrate moieties and it differs from the calcium-sensitive caseins in a number of respects. It is the only casein that is soluble in the presence of calcium ions and has a much smaller phosphate component than any of the other caseins. The phosphorylation sites are limited to the C-terminal region of the molecule and are present as single sites rather than the clusters found in the calcium-sensitive... 

The ETa receptor activates G proteins of the Gq/n and G12/i3 family. The ETB receptor stimulates G proteins of the G and Gq/11 family. In endothelial cells, activation of the ETB receptor stimulates the release of NO and prostacyclin (PGI2) via pertussis toxin-sensitive G proteins. In smooth muscle cells, the activation of ETA receptors leads to an increase of intracellular calcium via pertussis toxin-insensitive G proteins of the Gq/11 family and to an activation of Rho proteins most likely via G proteins of the Gi2/i3 family. Increase of intracellular calcium results in a calmodulin-dependent activation of the myosin light chain kinase (MLCK, Fig. 2). MLCK phosphorylates the 20 kDa myosin light chain (MLC-20), which then stimulates actin-myosin interaction of vascular smooth muscle cells resulting in vasoconstriction. Since activated Rho... 

IP3 receptor associated cGMP kinase substrate of 130 kDa that is present in all smooth muscles and platelets. It s phosphorylation decreases calcium release from intracellular EP3-sensitive stores. 

The T2 site also became protected from tryptic hydrolysis after phosphorylation of the native or solubilized sarcoplasmic reticulum vesicles with inorganic phosphate in a calcium free medium in the presence of dimethylsulfoxide or glycerol [121,252]. Under these conditions the Ca -ATPase is converted into a covalent E2-P intermediate, that is analogous in conformation to the E2V intermediate formed in the presence of vanadate. In contrast to this, the T2 site in the stable phosphorylated Ca2E P intermediate generated by the reaction of the Ca -ATPase with chro-mium-ATP in the presence of Ca [178,253] was fully exposed to trypsin, just as it was in the nonphosphorylated Ca2Ei form. Therefore the phosphorylated intermediates show the same sensitivity to trypsin at the T2 site as the corresponding nonphosphorylated enzyme forms. 

The immunotoxicology of metals in fishes has been reviewed elsewhere [74-76, 45], Overall, the immune systems of fishes are highly sensitive to metals, although the effects are not always suppression of immune functions. Burnett [76] demonstrated that low levels of metals increased intracellular calcium, increased protein phosphorylation, and stimulated lymphocyte proliferation in fish. Since most metals are toxic to both the nervous system and the immune system, a neuroendocrine-immune link to immuno-toxicity from metal exposure is likely. 

Alves AM, Symington SB, Lee SH, Clark JM (2010) PKC-dependent phosphorylations modify the action of deltamethrin on rat brain N-type (Cav2.2) voltage-sensitive calcium channel. Pestic Biochem Physiol 97 101-108... 

Inorganic phosphate is released when casein is heated. Dephosphor-ylated casein is less able to bind calcium and is more heat labile (Howat and Wright 1934). a9-Caseins are especially sensitive to the calcium concentration because of their high phosphorylation levels and small amounts of secondary and tertiary structure (Kinsella 1984). 

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