• Journal of Microbiology and Biotechnology
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• v.27 no.5
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• pp.878-895
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• 2017

Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.

• The Korean Journal of Zoology
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• v.16 no.2
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• pp.139-145
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• 1973

The activity of acid and alkaline phosphatases of pine moth, Dendrolimus spect abilis Butler was measured in a serier of developmental stages ranging from the larva to the adult. The activity of both enzymes increased gradually with age of larvae, and then decreased in the prepupal stage. Acid enzyme was at a maximum in the pupal early stage and alkaline enzyme in the 8th instar larva, respectively. And in the prepupal stage there were no significant differences between both acid and alkalnie phosphatases. However, their activities were far lower than in the 8th instar larva. In the pupal early stage there occurs a increase in the acitivity of acid enzyme followed by a decrease in the pupal later stage, and in the adult stage its activity increased again.

• Bulletin of the Korean Chemical Society
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• v.21 no.5
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• pp.515-517
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• 2000

• Bulletin of the Korean Chemical Society
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• v.27 no.10
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• pp.1567-1571
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• 2006

Synthetic color additives approved for general food use are sixteen in European Union, seven in U. S. A. and twelve in Japan. Twelve food dyes were examined for their inhibitory potency against human protein tyrosine phosphatases (PTPases). Half of the food colorants inhibited PTPases significantly and three of them were potent inhibitors with low micromolar IC50 values. Also examined were the synthetic dyes structurally similar but not allowed in food. Some of them were potent inhibitors of PTPases. Considering the importance of PTPases in cellular signal transduction, inhibition of PTPases by food colorants might cause harmful effects in human health.

• BMB Reports
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• v.46 no.6
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• pp.289-294
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• 2013

To maintain cellular homeostasis against the demands of the extracellular environment, a precise regulation of kinases and phosphatases is essential. In cell cycle regulation mechanisms, activation of the cyclin-dependent kinase (CDK1) and cyclin B complex (CDK1:cyclin B) causes a remarkable change in protein phosphorylation. Activation of CDK1:cyclin B is regulated by two auto-amplification loops-CDK1:cyclin B activates Cdc25, its own activating phosphatase, and inhibits Wee1, its own inhibiting kinase. Recent biological evidence has revealed that the inhibition of its counteracting phosphatase activity also occurs, and it is parallel to CDK1:cyclin B activation during mitosis. Phosphatase regulation of mitotic kinases and their substrates is essential to ensure that the progression of the cell cycle is ordered. Outlining how the mutual control of kinases and phosphatases governs the localization and timing of cell division will give us a new understanding about cell cycle regulation.

• BMB Reports
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• v.42 no.8
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• pp.467-474
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• 2009

The modification of proteins by reversible phosphorylation is a key mechanism in the regulation of various physiological functions. Abnormal protein kinase or phosphatase activity can cause disease by altering the phosphorylation of critical proteins in normal cellular and disease processes. Alzheimer' disease (AD), typically occurring in the elderly, is an irreversible, progressive brain disorder characterized by memory loss and cognitive decline. Accumulating evidence suggests that protein kinase and phosphatase activity are altered in the brain tissue of AD patients. Tau is a highly recognized phosphoprotein that undergoes hyperphosphorylation to form neurofibrillary tangles, a neuropathlogical hallmark with amyloid plaques in AD brains. This study is a brief overview of the altered protein phosphorylation pathways found in AD. Understanding the molecular mechanisms by which the activities of protein kinases and phosphatases are altered as well as the phosphorylation events in AD can potentially reveal novel insights into the role aberrant phosphorylation plays in the pathogenesis of AD, providing support for protein phosphorylation as a potential treatment strategy for AD.

• Bulletin of the Korean Chemical Society
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• v.21 no.1
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• pp.35-36
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• 2000

• Proceedings of the Zoological Society Korea Conference
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• 1996.04a
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• pp.42.1-42
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• 1996

No Abstract, See Full Text

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3669-3676
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• 2013

Faithful transmission of genetic information depends on accurate chromosome segregation as cells exit from mitosis, and errors in chromosomal segregation are catastrophic and may lead to aneuploidy which is the hallmark of cancer. In eukaryotes, an elaborate molecular control system ensures proper orchestration of events at mitotic exit. Phosphorylation of specific tyrosyl residues is a major control mechanism for cellular proliferation and the activities of protein tyrosine kinases and phosphatases must be integrated. Although mitotic kinases are well characterized, phosphatases involved in mitosis remain largely elusive. Here we identify a novel variant of mouse protein tyrosine phosphatase containing domain 1 (Ptpcd1), that we named Ptpcd2. Ptpcd1 is a Cdc14 related centrosomal phosphatase. Our newly identified Ptpcd2 shared a significant homology to yeast Cdc14p (34.1%) and other Cdc14 family of phosphatases. By subcellular fractionation Ptpcd2 was found to be enriched in the cytoplasm and nuclear pellets with catalytic phosphatase activity. By means of immunofluorescence, Ptpcd2 was spatiotemporally regulated in a cell cycle dependent manner with cytoplasmic abundance during mitosis, followed by nuclear localization during interphase. Overexpression of Ptpcd2 induced mitotic exit with decreased levels of some mitotic markers. Moreover, Ptpcd2 failed to colocalize with the centrosomal marker ${\gamma}$-tubulin, suggesting it as a non-centrosomal protein. Taken together, Ptpcd2 phosphatase appears a non-centrosomal variant of Ptpcd1 with probable mitotic functions. The identification of this new phosphatase suggests the existence of an interacting phosphatase network that controls mammalian mitosis and provides new drug targets for anticancer modalities.

• Molecules and Cells
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• v.24 no.2
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• pp.224-231
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• 2007

$H_2O_2$, as an example of oxidative stress, induces cardiac myocyte apoptosis. Bcl-2 family proteins are key regulators of the apoptotic response while their functions can be regulated by post-translational modifications including phosphorylation, dimerization or proteolytic cleavage. In this study, we examined the role of various protein kinases in regulating total BAD protein levels in adult rat cardiac myocytes undergoing apoptosis. Stimulation with 0.1 mM $H_2O_2$, which induces apoptosis, resulted in a marked down-regulation of BAD protein, which is attributed to cleavage by caspases since it can be restored in the presence of a general caspase inhibitor. Inhibition of PKC, p38-MAPK, ERK1/2 and PI-3-K did not influence the reduced BAD protein levels observed after stimulation with $H_2O_2$. On the contrary, inhibition of PKA or specifically $PKC{\delta}$ resulted in up-regulation of BAD. Decreased caspase 3 activity was observed in $H_2O_2$ treated cells after inhibition of PKA or $PKC{\delta}$ whereas inhibition of PKA also resulted in improved cell survival. Furthermore, addition of okadaic acid to inhibit selected phosphatases resulted in enhanced BAD cleavage. These data suggest that, during oxidative stress-induced cardiac myocyte apoptosis, there is a caspase-dependent down-regulation of BAD protein, which seems to be regulated by coordinated action of PKA, $PKC{\delta}$ and phosphatases.