Phosphatases, phosphoprotein

Reversibility in signalling requires that ultimately phosphoproteins must be dephosphory-lated. This is achieved by PPs that catalyse the following hydrolysis reaction  

In addition to the P-Ser- and P-Thr-specific PPs described above, there are a number of P-Tyr-specific PPases that reverse the consequences of protein Tyr phosphorylation deriving from RTK and TK activation. Substrates include RTKs themselves and downstream Tyr-phosphorylated signalling proteins such as PKCy, MAPK (ERK), JAK/STAT receptors, kinases, STATs and the CDKs described above. 

Compound (class) Plant source (family) / plant part/ Target inhibited (other targets) 

Earl Sutherland (USA, Nobel 8.1 Prize, Medicine, 1971 cAMP as Yuichiro Nishizuka (Japan, second messenger) Paul PKC), Phillip Cohen (UK, 

2001 (CDK)) with Tim Hunt (UK, cyclins) Leland Hartwell (USA, CDC genes)  

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Dephosphorylation of glycogen phosphorylase is carried out by phospho-protein phosphatase 1. The action of phosphoprotein phosphatase 1 inactivates glycogen phosphorylase. 

Phosphonoacetic acid antiviral activity, 6, 771 Phosphoprotein phosphatases activation... 

Figure 2. Mechanism of PDH. The three different subunits of the PDH complex in the mitochondrial matrix (E, pyruvate decarboxylase E2, dihydrolipoamide acyltrans-ferase Ej, dihydrolipoamide dehydrogenase) catalyze the oxidative decarboxylation of pyruvate to acetyl-CoA and CO2. E, decarboxylates pyruvate and transfers the acetyl-group to lipoamide. Lipoamide is linked to the group of a lysine residue to E2 to form a flexible chain which rotates between the active sites of E, E2, and E3. E2 then transfers the acetyl-group from lipoamide to CoASH leaving the lipoamide in the reduced form. This in turn is oxidized by E3, which is an NAD-dependent (low potential) flavoprotein, completing the catalytic cycle. PDH activity is controlled in two ways by product inhibition by NADH and acetyl-CoA formed from pyruvate (or by P-oxidation), and by inactivation by phosphorylation of Ej by a specific ATP-de-pendent protein kinase associated with the complex, or activation by dephosphorylation by a specific phosphoprotein phosphatase. The phosphatase is activated by increases in the concentration of Ca in the matrix. The combination of insulin with its cell surface receptor activates PDH by activating the phosphatase by an unknown mechanism.

Regulation of L-type channels by phosphoprotein phosphatases As phosphorylation of certain Ca channels by protein kinases has been shown to... 

A few enzymes, such as the previously mentioned CNP, are believed to be fairly specific for myelin/oligodendro-cytes. There is much more in the CNS than in peripheral nerve, suggesting some function more specialized to the CNS. In addition, a unique pH 7.2 cholesterol ester hydrolase is also enriched in myelin. On the other hand, there are many enzymes that are not myelin-specific but appear to be intrinsic to myelin and not contaminants. These include cAMP-stimulated kinase, calcium/calmodulin-dependent kinase, protein kinase C, a neutral protease activity and phosphoprotein phosphatases. The protein kinase C and phosphatase activities are presumed to be responsible for the rapid turnover of MBP phosphate groups, and the PLP acylation enzyme activity is also intrinsic to myelin. 

A calmoduhn-binding phosphoprotein phosphatase, found at highest abundance in brain tissue, that removes... 

PHOSPHOPROTEIN PHOSPHATASES SERPINS (INHIBITORY MECHANISM) L-SERYL-tRNA - SELENIUM TRANSFERASE l-SELENOCYSTEINE Severing protein,... 

Milk acid phosphatase has been purified to homogeneity by various forms of chromaotgraphy, including affinity chromatography purification up to 40 000-fold has been claimed. The enzyme shows broad specificity on phosphate esters, including the phosphoseryl residues of casein. It has a molecular mass of about 42 kDa and an isoelectric point of 7.9. Many forms of inorganic phosphate are competitive inhibitors, while fluoride is a powerful non-competitive inhibitor. The enzyme is a glycoprotein and its amino acid composition is known. Milk acid phosphatase shows some similarity to the phosphoprotein phosphatase of spleen but differs from it in a number of characteristics. 

Shiao, M.-S. Drong, R.F. Porter, J.W. The purification and properties of a protein kinase and the partial purification of a phosphoprotein phosphatase that inactivate and activate acetyl-CoA carboxylase. Biochem. Biophys. Res. Commun., 98, 80-87 (1981)... 

Lieberherr, M., Vreven, J., Vaes, G. The acid and alkaline phosphatases, inorganic pyrophosphatases and phosphoprotein phosphatase of bone. I. Characterization and assay. Bio-chim. Biophys. Acta 293, 160 (1973)... 

To serve as an effective regulatory mechanism, phosphorylation must be reversible. In general, phos-phoryl groups are added and removed by different enzymes, and the processes can therefore be separately regulated. Cells contain a family of phosphoprotein phosphatases that hydrolyze specific -Ser, -Thr, and -Tyr esters, releasing Pj. The phosphoprotein phosphatases we know of thus far act only on a subset of phosphoproteins, but they show less substrate specificity than protein kinases. 

Glucagon or epinephrine decreases [fructose 2,6-bisphosphate]. The hormones do this by raising [cAMP] and bringing about phosphorylation of the bifunctional enzyme that makes and breaks down fructose 2,6-bisphosphate. Phosphorylation inactivates PFK-2 and activates FBPase-2, leading to breakdown of fructose 2,6-bisphosphate. Insulin increases [fructose 2,6-bisphosphate] by activating a phosphoprotein phosphatase that dephosphorylates (activates) PFK-2. 

Some bacteria, including E. coli, have the full complement of enzymes for the glyoxylate and citric acid cycles in the cytosol and can therefore grow on acetate as their sole source of carbon and energy. The phosphoprotein phosphatase that activates isocitrate dehydrogenase is stimulated by intermediates of the citric acid cycle and glycolysis and by indicators of reduced cellular energy supply (Fig. 16-23). The same metabolites inhibit the protein kinase activity of the bifunctional polypeptide. Thus, the accumulation of intermediates of... 

Phosphorylation and dephosphorylation Phosphorylation reactions are catalyzed by a family of enzymes called protein kinases that use adenosine triphosphate (ATP) as a phosphate donor. Phosphate groups are cleaved from phosphorylated enzymes by the action of phosphoprotein phosphatases (Figure 5.18). 

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