Protein phosphatase-1 , activation

Semiz, S. and J.H. McNeill. 2002. Oral treatment with vanadium of Zucker fatty rats activates muscle glycogen synthesis and insulin-stimulated protein phosphatase-1 activity. Mol. Cell. Biochem. 236 123-131. 

Protein phosphatase-1. Activated by insulin-generated signals... 

For in vitro studies there are a number of compounds available to block protein phosphatase activity. Phosphate buffers inactivate all of these enzymes. Several naturally occurring toxins are potent inhibitors of PPPs, e.g., okadaic acid or microcystin, and are frequently used tools. PPM and PTP family members are not affected by these toxins. Vanadate containing solutions are competitive inhibitors of PTPs, pervanadate is an irreversible inhibitor of PTPs. 

Microcystins are extremely potent inhibitors of protein phosphatases, active at the level of 0.2 nM (2 x 10-10 M). Coupled with the active uptake into the liver, this means that microcystins are extremely toxic. As well as being hepatotoxic, they are also tumor promoters. 

Swarup, G., S. Cohen, and D.L. Garbers. 1982. Inhibition of membrane phosphoty-rosyl-protein phosphatase activity by vanadate. Biochem. Biophys. Res. Commun. 107 1104-1109. 

Intracellular signaling Increased protein kinase C activity or decreased protein phosphatase activity Slaga et al. [15] Anti-CD3 activates mitogen-activated kinase Erk2 Von Willebrand et al. [110]... 

Dihydroceramide exhibits different physical and biochemical effects compared with the corresponding ceramide bearing the same A-acyl chain. For example, channel formation in mitochondrial membranes (78) and protein phosphatase activity in pancreatic beta cells are inhibited by dihydroceramide but are activated by ceramide (63, 79). Dihydroceramide is less effective than ceramide in inducing apoptosis (68). 

Another important point from the HePTP case study illustrates epistemic challenges and their resolution with the use of small-molecule chemical probes. Although reversible oxidation of the phosphatase active site cysteines was hypothesized as one of the cellular pathways regulating protein phosphatase activity prior to our studies [40, 41], this mechanism was not experimentally demonstrated for HePTP. Identified small-molecule hits not only enabled biologically relevant inhibition of HePTP but also pointed... 

The phospho-opsin phosphatase from bovine rod outer segments. An insight into the mechanism of stimulation of type-2A protein phosphatase activity by protamine. Eur J Biochem 225 383-394... 

Some transmembrane receptors have cytoplasmic protein phosphatase activity. Soluble protein phosphatases, such as calcineurin, PP1, PP2A, PP2C, and protein tyrosine phosphatases, also mediate intracellular signals. 

Ishihara H, Martin BL, Brautigan DL, Karaki H, Ozaki H, Kato Y, Fusetani N, Watabe S, Hashimoto K, Uemura D, Hartshorne DJ (1989) Calyculin A and okadaic acid inhibitors of protein phosphatase activity. Biochem Biophys Res Commun 159 871-877... 

Toward understanding the mechanistic action of toxicology using 2DE, Foun-toulakis et al. showed the hepatotoxic effects of paracetamol (acetaminophen) overdose in human and rodent liver [74]. They found that the expression of 35 proteins was altered after treatment with paracetamol or its nontoxic regioisomer 3-acetamidophenol. Paracetamol selectively increases or decreases the phosphorylation state of proteins. This effect translates to a decrease in protein phosphatase activity [80]. The control of cellular functions of cells may be lost as a result of the dephosphorylation of certain regulatory proteins due to paracetamol overdose. 

Bruno M K, Khairallah E A, Cohen S D (1998). Inhibition of protein phosphatase activity and changes in protein phosphorylation following acetaminophen exposure in cultured mouse hepatocytes. Toxicol. Appl. Pharm. 153 119-132. 

Eriksson, J.E. et al., Cytoskeletal integrity in interphase cells requires protein phosphatase activity, Proc. Natl. Acad. Sci. USA, 89, 11093, 1992. 

Yan, Y. et al.. Inhibition of protein phosphatase activity induces p53-dependent apoptosis in the absence of p53 transactivation, J. Biol Chem., 272, 15220, 1997. 

Yamashita, K. et ah, Okadaic acid, a potent inhibitor of type 1 and type 2 protein phosphatase, activates cdc2/Hl kinase and transiently induces a premature mitosis-like state in BHK21 cells, EMBO J., 9,4331, 1990. 

Swain JE, Ding J, Brautigan DL, ViUa-Moruzzi E, Smith GD. 2007. Proper chromatin condensation and maintenance of histone H3 phosphorylation during mouse oocyte meiosis requires protein phosphatase activity. Biol Reprod 76(4) 628-638. 

For high-performance separation methods suffering of insufficient detectability in determination of MC in environmental samples for routine applications the most effective is preconcentration on immunosorbents. The new advantageous competitors in this field might be enzymatic assays and biosensors based on inhibition of protein phosphatase activity by MC. Some successful attempts in this field have been reported recently as colorimetric assays or electrochemical biosensors. 

Geladopoulos, T. P., Sotiroudis, T. G., and Evangelopoulos, A. E. (1991). A malachite green colorimetric assay for protein phosphatase activity. Anal. Biochem. 192,112-116. 

Three protein phosphatase activities have been isolated from rabbit skeletal muscle protein phosphatase I (mol. wt. 3 x 10 , an active histone phosphatase) exhibited only little glycogen synthase phosphatase-1 and -2, phosphorylase... 

Ruan Y, Cheng M, Ou Y, Oko R, van der Hoorn FA (2011) Ornithine decarboxylase antizyme Oaz3 modulates protein phosphatase activity. J Biol Chem 286 29417-29427... 

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