• Bulletin of the Korean Chemical Society
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• 제31권12호
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• pp.3812-3814
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• 2010

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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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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• 제19권3호
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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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• 제33권1호
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• pp.275-277
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• 2012

• 대한약리학회지
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• 제32권1호
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• pp.103-112
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• 1996

Platelet-activating factor (PAF)에 의하여 자극된 호중구 respiratory burst, 탈과립과 세포질 칼슘농도의 증가에 있어 protein kinase C와 protein tyrosine kinase의 역할을 관찰하였다. PAF에 의하여 자극된 호중구에서 superoxide 및 $H_2O_2$의 생성과 myeloperoxidase와 acid phosphatase의 유리는 protein kinase C 억제제인 staurosporine과 H-7 그리고 protein tyrosine kinase 억제제인 genistein과 tyrphostin에 의하여 억제되었다. PAF에 의한 호중구 세포내 칼슘농도의 증가는 staurosporine, genistein과 methyl-2,5-dihydroxycinnamate에 의하여 억제 되었다. Staurosporine은 PAF에 의하여 자극된 호중구에서 세포내 칼슘유리와 망간유입을 억제 하였다. Genistein과 methyl-2,5-dihydroxycinnamate는 PAF에 의한 망간유입을 억제하였으나, 세포내 칼슘유리에 대한 이들의 효과는 관찰되지 않았다. PMA에 의하여 활성화된 호중구에서 세포내 칼슘농도의 증가에 대한 PAF의 자극효과는 감소되었다. Protein kinase C와 protein tyrosine kinase는 PAF에 의하여 자극된 호중구에서의 respiratory burst, lysosomal enzyme유리와 칼슘동원에 관여할 것으로 제시된다. 세포내 칼슘농도의 증가는 protein kinase의 영향을 다르게 받는 세포내 칼슘유리와 세포외부로 부터의 칼슘유입에 의하여 이루어질 것으로 추정된다. Protein kinase C가 활성화되어 있는 상태에서 세포내 칼슘동원에 대한 PAF의 자극작용은 감소될 것으로 시사된다.

• Bulletin of the Korean Chemical Society
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• 제32권spc8호
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• pp.2883-2884
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• 2011

• BMB Reports
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• 제34권6호
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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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• 제3권3호
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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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• 대한약리학회 2006년도 The 6th Congress of the Federation of Asian and Oceanian Physiological Societies
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• pp.92.2-92.2
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• 2006

• Applied Biological Chemistry
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• 제51권3호
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• pp.171-176
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• 2008

기질 화합물로써 3${\beta}$-Hydroxy-12-oleanen-28-oic acid 유도체(1-30)들과 그들의 protein tyrosine phosphatase(PTP)-1B 저해활성에 관한 비교분자 유사성 지수분석(CoMSIA)보델을 유도하였다. QSAR 모델의 통계 값은 CoMFA>CoMSIA${\geq}$HQSAR>2D-QSAR 모델의 순서로 양호하였다. 최적화된 CoMSIA F1 모델은 grid 3.0${\AA}$과 field fit 정렬조건에서 가장 족은 예측성과 상관성($r^2_{cf}$=0.754 및 $r^2_{ncv}$=0.976)을 나타내었다. 저해 활성에 관한 CoMSIA상의 기여비율(%)은 수소결합 받게장(48.9%), 입체장(25.8%) 및 소수성장(25.4%)의 순서이었다. 그러므로 기질 화합물의 PTP-1B에 대한 저해활성은 $R_4$-치환기의 수소결합 받게 장(A)에 의존적이었다. 등고도 분석 결과로부터 $R_1$-치환기는 수소결합 받게장이 작고 $R_3$-치환기는 입체장이 작으며 그리고 $R_4$-치환기는 수소결합 받게장, 소수성 및 입체장이 큰 치환기가 저해활성을 증가시킬 것으로 예측되었다.