• Bulletin of the Korean Chemical Society
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• v.31 no.12
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• pp.3812-3814
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• 2010

• 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.

• ALGAE
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• v.19 no.3
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• pp.271-276
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• 2004

One hundred and fifty four micro algal strains, newly isolated from nationwide freshwaters in Korea, were screened for their anticancer, ant diabetic, and antibiotic activities. The micro algal strains were cultured with different nutritional conditions that were divided into 4 groups as follows; a normal Allen medium, nitrogen (N)-limited medium, phosphorus (P)-limited medium, and N and P-limited medium. Algal biomass was extracted with a mixture of acetone:H₂O (1:1, v:v) and the extracts were used for the screening of bioactive materials. Anticancer, ant diabetic, and antibiotic materials were screened by the methods of vaccinia Hl-related protein tyrosine phosphates (VHR DS-PTPase) inhibition, protein tyrosine phosphates 1B (PTP1B) inhibition, and paper disk. The inhibition activity of VHR DS-PTPase was observed in 18 strains, having a maximum 79% inhibition from Anabaena affinis and the inhibition activity of PTP1B was observed in 9 strains, having a maximum 97% from Sphaerocystis schroeteri. Microcystis aeruginosa incubated in an N and P-limited medium showed antibiotic activity in 8 species out of 13 pathogenic bacteria. As a whole, it seemed that the stressed condition such as N and/or P limitation increased the production of bioactive materials in micro algae.

• Bulletin of the Korean Chemical Society
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• v.33 no.1
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• pp.275-277
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• 2012

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.103-112
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• 1996

Roles of protein kinase C and protein tyrosine kinase in the activation of neutrophil respiratory burst, degranulation and elevation of cytosolic $Ca^{2+}$ in platelet-activating factor (PAF)-stimulated neutrophils were investigated. Superoxide and $H_2O_2$ production and myeloperoxidase and acid phosphatase release in PAF-stimulated neutrophils were inhibited by protein kinase C inhibitors, staurosporine and H-7 and protein tyrosine kinase inhibitors, genistein and tyrphostin. The PAF-induced elevation of $[Ca^{2+}]_i$ in neutrophils was inhibited by staurosporine, genistein and methyl-2,5-dihydroxycinnamate. Staurosporine inhibited both intracellular $Ca^{2+}$ release and $Mn^{2+}$ influx in PAF-stimulated neutrophils. Genistein and methyl-2,5-dihydroxycinnamate inhibited $Mn^{2+}$ influx induced by PAF, whereas their effects on intracellular $Ca^{2+}$ release were not detected. In neutrophils preactivated by PMA, the stimulatory effect of PAF on the elevation of $[Ca^{2+}]_i$ was reduced. Protein kinase C and protein tyrosine kinase may be involved in respiratory burst, lysosomal enzyme release and $Ca^{2+}$ mobilization in PAF-stimulated neutrophils. The elevation of $[Ca^{2+}]_i$ appears to be accomplished by intracullular $Ca^{2+}$ release and $Ca^{2+}$ influx which are differently regulated by protein kinases. Preactivation of protein kinase C appears to attenuate the stimulatory action of PAF on intracellular $Ca^{2+}$ mobilization.

• Bulletin of the Korean Chemical Society
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• v.32 no.spc8
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• pp.2883-2884
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• 2011

• BMB Reports
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• v.34 no.6
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• pp.517-525
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• 2001

Six renaturable protein kinases that utilize the myelin basic protein (MBP) as a substrate were activated during prolonged exposure of cardiac myocytes to okadaic acid (OA). We characterized the substrate preference and activation of these kinases, with particular emphasis on 3 novel kinases-MBPK-55, MBPK-62 and MBPK-87. The transcription factors c-Jun, Elk, ATF2, and c-Fos that are used to assess mitogen-activated protein kinase activation were all poor substrates for these three kinases. MAPKAPK2 was also not phosphorylated. In contrast, Histone IIIS was phosphorylated by MBPK-55 and MBPK-62. These protein kinases were activated in cultured cardiac fibroblasts, H9c2 cardiac myoblasts, and Cos cells. High concentrations (0.5 to $1\;{\mu}M$) of OA were essential for the activation of the protein kinases in all of the cell types examined, whereas calyculin A [an inhibitor of protein phosphatase 1 (PP1) and PP2A], cyclosporin A (a PP2B inhibitor), and an inactive OA analog all failed to activate these kinases. The high dose of okadaic acid that is required for kinase activation was also required for phosphatase inhibition, as assessed by immunoblotting whole cell lysates with anti-phosphothreonine antibodies. A variety of chemical inhibitors, including PD98059 (MEK-specific), genistein (tyrosine kinase-specific) and Bisindolylmaleimide I (protein kinase C-specific), failed to inhibit the OA activation of these kinases. Thus, MBPK-55 and MBPK-62 are also Histone IIIS kinases that are widely expressed and specifically activated upon exposure to high OA concentrations.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.293-303
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• 1999

The influences of specific protein phosphatase and protein kinase inhibitors on the ATP-sensitive $K^+\;(K_{ATP})$ channel-opening effect of pinacidil were investigated in single rat ventricular myocytes using patch clamp technique. In cell-attached patches, pinacidil $(100\;{\mu}M)$ induced the opening of the $K_{ATP}$ channel, which was blocked by the pretreatment with H-7 $(100\;{\mu}M)$ whereas enhanced by the pretreatment with genistein $(30\;{\mu}M)$ or tyrphostin A23 $(10\;{\mu}M)$. In inside-out patches, pinacidil $(10\;{\mu}M)$ activated the $K_{ATP}$ channels in the presence of ATP (0.3 mM) or AMP-PNP (0.3 mM) and in a partial rundown state. The effect of pinacidil $(10\;{\mu}M)$ was not affected by the pretreatment with protein tyrosine phosphatase 1B $(PTP1B,\;10\;{\mu}g\;ml^{-1}),$ but blocked by the pretreatment of protein phosphatase 2A $(PP2A,\;1\;U\;ml^{-1})$. In addition, pinacidil $(10\;{\mu}M)$ could not induce the opening of the reactivated $K_{ATP}$ channels in the presence of H-7 $(100\;{\mu}M)$ but enhanced it in the presence of ATP (1 mM) and genistein $(30\;{\mu}M).$ These results indicate that the $K_{ATP}$ channel-opening effect of pinacidil is not mediated via phosphorylation of $K_{ATP}$ channel protein or associated protein, although it still requires the phosphorylation of serine/threonine residues as a prerequisite condition.

• 대한약리학회:학술대회논문집
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• 2006.10a
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• pp.92.2-92.2
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• 2006

• Applied Biological Chemistry
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• v.51 no.3
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• pp.171-176
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• 2008

The comparative molecular similarity indices analysis (CoMSIA) models between 3${\beta}$-Hydroxy-12-oleanen-28-oic acid (1-30) analogues as substrate molecule and their inhibitory activities ($pI_{50}$) against protein tyrosine phosphatase (PTP)-1B were derived and discussed quantitatively. Listing in order, the CoMFA>CoMSIA${\geq}$HQSAR>2D-QSAR model, these QSAR models had the better statistical values. The optimized CoMSIA F1 model at grid 3.0${\AA}$ had the best predictability and fitness ($q^2$=0.754 and $r^2$=0.976) by field fit alignment. The order of contribution ratio (%) of CoMSIA fields concerning the inhibitory activities was a H-bond acceptor (48.9%), steric field (25.8%) and hydrophobic field (25.4%), respectively. Therefore, the inhibitory activities of substrate molecules against PTP-1B were dependent upon H-bond acceptor field (A) of $R_4$-group. From the analytical results of CoMSIA contour maps, oleanolic acid derivatives will have better inhibition activities if $R_1$ group has H-bond acceptor disfavor, $R_3$group has steric disfavor and $R_4$ group has steric, hydrophobic, H-bond favor.