Phosphatase, dephosphorylation

Signaling by PKC is terminated by concentrations of its ligands dropping to basal levels (i.e., Ca2+ and diacylglycerol) and by dephosphorylation of the three processing sites. Dephosphorylation is controlled, in part, by a recently discovered hydrophobic phosphorylation motif phosphatase. This phosphatase, PHLPP (for PH domain Leucine-rich repeat Protein Phosphatase) dephosphorylates conventional and novel PKC isozymes, initiating their downregulation. 

Since the enzyme glycogen synthase catalyses the rate-limiting step in glycogen synthesis, it is the activity of this enzyme that must be increased as the blood glucose concentration increases. This is achieved via an interconversion cycle (i.e. reversible phosphorylation). A protein kinase phosphorylates it, which inactivates the enzyme, whereas a protein phosphatase dephosphorylates it, which... 

Cellular levels of fructose-2,6-biphosphate, the positive effector of PFK I, are increased when blood insulin levels are high because PFK II is active as a result of a suppression of fructose-2,6-biphosphate phosphatase (dephosphorylation) and activation (dephosphorylation) of PFK II. 

Insulin also exerts a stimulatory effect on the synthesis of cholesterol in the liver. In this tissue, HMG-CoA reductase is activated. HMG-CoA reductase, like hormone-sensitive lipase, can exist in two forms one is phosphorylated (inactive) and the other is dephosphorylated (active). Phosphorylation of the enzyme depends on an increase in the cellular concentration of cAMP and activation of protein kinase. The dephosphorylation (activation) is catalyzed by a phosphatase. In fat cells, a similar phosphatase dephosphorylates (inactivates) hormone-sensitive lipase. Insulin stimulates the activity of the phosphatase in both liver and fat cells. In this way, active HMG-CoA reductase predominates in the liver cell and directs HMG-CoA into cholesterol synthesis, and in the fat cell hormone-sensitive lipase is inactivated. 

Phosphotyrosine phosphatases dephosphorylate JAKs and silence receptor-JAK complexes. They also inactivate JAKs which have been released from the receptor complex and are out of control. But dephosphorylation of tyrosines may also have positive effects and enhance cytokine signalling. A related phosphotyrosine phosphatase, actually stimulates IL-6 signalling, suggesting that the phosphotyrosines in the IL-6 receptor-JAK complex, which are attacked by the phosphatase, are inhibitory. The phosphatase activi-... 

In the fed state, insulin causes phosphatases to be stimulated. A phosphatase dephosphorylates PFK2, causing it to become more active in forming fructose 2,6-bisphosphate from fructose 6-phosphate. Fructose 2,6-bisphosphate levels rise, and PFK1 is more active. 

Several topoisomerases have been shown to be substrates for protein kinases. Nuclear extracts from a human cell line contain a protein kinase which phosphorylates DNA topoisomerase I from the same cell line (Mills et al., 1982). The type I topoisomerase purified from Novikoff hepatoma cells was found to be a phosphoprotein (Durban et al., 1983). Treatment with alkaline phosphatase dephosphorylates the enzyme and reduces its DNA-relaxing activity. Subsequent treatment with protein kinase restores the activity of the topoisomerase to its original level (Durban et al., 1983). 

LC20 phosphatase dephosphorylates LC20. This is a trimeric type I protein phosphatase (PP-I) comprising a catalytic subunit (M.W. 37,000), a myosin-binding subunit (M.W. 130,000), and a 20,000-M.W. subunit that also binds myosin. This PP-I may be inhibited by high arachi-donic acid, and inhibited or stimulated by phosphorylation... 

Corcoran NM, Martin D, Hutter-Paier B et al (2010) Sodium selenate specifically activates PP2A phosphatase, dephosphorylates tau and reverses memory deficits in an Alzheimer s disease model. J Cfin Neturosci 17 1025-1033... 

Dephosphorylation. In vivo, phosphoprotein phosphatases (phos-phoprotein phosphohydrolase EC 3.1.3.16) participate in the regulation of phosphate turnover and in rapid reversal of the phosphorylating reactions, yet there is very little information on this important group of enzymes. Alkaline (104) and acid (105) phosphatases of milk can hydrolyze the phosphate groups of phosphoserine residues in the caseins. E. coli alkaline phosphatase dephosphorylates many phosphoproteins (106,107). A phosphoprotein phosphatase of liver dephosphorylates phosphorylated histones and protamines but has little or no activity on casein or phosvitin (108). The 60-fold purified enzyme had an apparent Km for dephosphorylation of histone I (FI) of 2 X 10"5M and a pH optimum of 7-8. Histone phosphatase activity was detected in all eukaryotic cells examined, but it was not found in the extracts of several prokaryotes. 

Consensus sites for phosphorylation were evident in the neuronal NOS enzyme from the predicted protein sequences derived from cDNA analysis. In vitro biochemical studies indicate that nNOS can be phosphorylated by calcium/calmodulin-dependent protein kinase, cAMP-dependent protein kinase, cGMP-dependent protein kinase, and protein kinase C. Phosphorylation of nNOS by all of these enzymes decreases NOS catalytic activity in vitro (Dawson and Snyder, 1994 Bredt etal., 1992 Dinerman etal., 1994a). Calcineurin, a protein phosphatase, dephosphorylates NOS and subsequently increases its catalytic activity (T. M. Dawson etal., 1993). Multiple levels of constitutive nNOS regulation are thus possible by phosphorylation. 

A phosphatase dephosphorylates glycogen phosphorylase and glycogen synthetase, inactivating and activating them, respectively. The phosphatase becomes active in response to high concentrations of glucose. 

Insulin results in the activation of PPl. The hormone activates an insulin-sensitive protein kinase that phosphorylates a subunit of PPl, rendering the phosphatase more active. The activated phosphatase dephosphorylates phosphorylase, protein kinase, and glycogen synthase. These changes result in a decrease in glycogen degradation and the stimulation of glycogen synthesis. 

A thylakoid bound protein kinase,ac ivated when PCH2 and/or cyt.b563 are extensively reduced, phosphorylates LEfC-II and a thylakoid bound phosphatase dephosphorylates it (1,2,3). The phosphorylatiai-... 

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