• Journal of Microbiology and Biotechnology
• /
• 제19권9호
• /
• pp.918-921
• /
• 2009

In the present study, we examined the inhibitory effects of protein tyrosine phosphatase (PTPase) inhibitors, including sodium orthovanadate (SOV), ammonium molybdate (AM), and iodoacetamide (IA), on cell growth, accumulation of astaxanthin, and PTPase activity in the photosynthetic algae Haematococcus lacustris. PTPase activity was assayed spectrophotometrically and was found to be inhibited 60% to 90% after treatment with the inhibitors. SOY markedly abolished PTPase activity, significantly activating the accumulation of astaxanthin. These data suggest that the accumulation of astaxanthin in H. lacustris results from the concerted actions of several PTPases.

• Molecules and Cells
• /
• 제27권3호
• /
• pp.345-350
• /
• 2009

We previously reported that flavone induces embryonic lethality in Caenorhabditis elegans, which appeared to be the result of cell cycle arrest during early embryogenesis. To test this possibility, here we examined whether flavone inhibits the activity of a key cell cycle regulator, CDC-25.1 in C. elegans. A gain-of-function cdc-25.1 mutant, rr31, which exhibits extra cell divisions in intestinal cells, was used to test the inhibitory effects of flavone on CDC-25 activity. Flavone inhibited the extra cell divisions of intestinal cells in rr31, and modifications of flavone reduced the inhibitory effects. The inhibitory effects of flavone on CDC-25.1 were partly, if not completely, due to transcriptional repression.

• BMB Reports
• /
• 제46권10호
• /
• pp.490-494
• /
• 2013

The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor-suppressing lipid phosphatase that is frequently absent in breast tumors. Thus, the stability of PTEN is essential for tumor prevention and therapy. The ubiquitin-proteasome pathway has an important role in regulating the functions of PTEN. Specifically, carboxyl terminus Hsp70-interacting protein (CHIP), the E3 ubiquitin ligase of PTEN, can regulate PTEN levels. In this study, we report that BCL-2-associated athanogene 5 (BAG5), a known inhibitor of CHIP activity, reduces the degradation of PTEN and maintains its levels via an ubiquitylation-dependent pathway. BAG5 is identified as an antagonist of cell tumorigenicity.

• Bulletin of the Korean Chemical Society
• /
• 제25권8호
• /
• pp.1121-1122
• /
• 2004

• Bulletin of the Korean Chemical Society
• /
• 제33권11호
• /
• pp.3772-3776
• /
• 2012

Mitogen-activated protein kinase phosphatase 4 (MKP4) has proved to be a promising target for the development of therapeutics for the treatment of diabetes and the other metabolic diseases. Here, we report an example for a successful application of the structure-based virtual screening to identify three novel inhibitors of MKP4. These inhibitors have desirable physicochemical properties as a drug candidate and reveal a moderate potency with $IC_{50}$ values ranging from 4.9 to $32.3{\mu}M$. Therefore, they deserve consideration for further development by structure-activity relationship studies to optimize the inhibitory and antidiabetic activities. Structural features relevant to the stabilization of the newly identified inhibitors in the active site of MKP4 are discussed in detail.

• 통합자연과학논문집
• /
• 제11권1호
• /
• pp.25-29
• /
• 2018

Protein phosphatase manganese dependent 1D (PPM1D), a Ser/Thr protein phosphatise, play major role in the cancer tumorigenesis of various tumors including neuroblastoma, pancreatic adenocarcinoma, medulloblastoma, breast cancer, prostate cancer and ovarian cancer. Hence, analysis on the structural features required for the formation of PPM1D-inhibitor complex becomes essential. In this study, we have performed molecular docking of SL-175 and -176 and protein-protein docking of CDC5L with PPM1D. On analysing the docked complexes, we have identified the important residues involved in the formation of protein-ligand complex. Research concentrating on these residues could be helpful in understanding the pathophysiology of various tumors related to PPM1D.

• 생약학회지
• /
• 제20권3호
• /
• pp.154-161
• /
• 1989

Effects of panaxydol, panaxynol and panaxytriol isolated from Panax ginseng C.A. Meyer on some enzyme activities were determined. Activities of ATPase, membrane-bound enzyme from Sarcoma 180 and rat liver were slightly inhibited by panaxydol. Activities of 5'-nucleotidase, membrane-bound enzyme and succinate cytochrome c reductase in mitochonidria from sarcoma 180 and rat livers were significantly inhibited in a dose-dependent manner by panaxynol. The inhibitory effects of panaxydol and panaxynol on succinate cytochrome c reductase activities were more potent than those on 5'-nucleotidase activities and panaxynol was found to be a very potent inhibitor of succinate cytochrome c reductase. Activities of glucose-6-phosphatase in endoplasmic reticulum from Sarcoma 180 and rat livers were not affected by all three polyacetylenes. These results suggested that the inhibitory effects of panaxydol and panaxynol on enzyme activities might contribute to their biological activities.

• Bulletin of the Korean Chemical Society
• /
• 제34권8호
• /
• pp.2487-2490
• /
• 2013

SA51, a medium potency inhibitor of protein tyrosine phosphatase 1B (PTP1B), was identified to be a potent inhibitor of $I{\kappa}B$ kinase ${\beta}$ ($IKK{\beta}$). Consistent with this, SA51 prevented lipopolysaccharide (LPS)-induced breakdown of $I{\kappa}B{\alpha}$ in macrophages. The effects of SA51 in mice were compared with those of structurally related compounds, SA18 and SA32, which were previously reported as inhibitors of both enzymes - less potent against $IKK{\beta}$ but more potent against PTP1B compared to SA51. SA51 improved glucose tolerance and lipid parameters in mice, consistent with the results reported for $IKK{\beta}^{+/-}$ mice. In contrast, SA18 and SA32 showed anti-obesity effects without anti-diabetic effects. Collectively, the effects of SA51 could be due largely to the inhibition of $IKK{\beta}$, whereas SA18 and SA32 may be more likely to inhibit PTP1B, consistent with their relative in vitro inhibitory effects.

• The Korean Journal of Physiology and Pharmacology
• /
• 제2권6호
• /
• pp.743-752
• /
• 1998

The atrial acetylcholine-activated $K^+\;(K_{ACh})$ channel is gated by the pertussis toxin-sensitive inhibitory G $(G_K)$ protein. Earlier studies revealed that ATP alone can activate the $K_{ACh}$ channel via transphosphorylation mediated by nucleoside-diphosphate kinase (NDPK) in atrial cells of rabbit and guinea pig. This channel can be activated by various agonists and also modulated its function by phosphorylation. ATP-induced $K_{ACh}$ channel activation (AIKA) was maintained in the presence of the NDPK inhibitor, suggesting the existence of a mechanism other than NDPK-mediated process. Here we hypothesized the phosphorylation process as another mechanism underlying AIKA and was undertaken to examine what kinase is involved in atrial cells isolated from the rat heart. Single application of 1 mM ATP gradually increased the activity of $K_{ACh}$ channels and reached its maximum $40{\sim}50$ sec later following adding ATP. AIKA was not completely reduced but maintained by half even in the presence of NDPK inhibitor. Neither ADP nor a non-hydrolyzable ATP analogue, AMP-PNP can cause AIKA, while a non-specific phosphatase, alkaline phosphatase blocked completely AIKA. PKC antagonists such as sphingosine or tamoxifen, completely blocked AIKA, whereas PKC catalytic domain increased AIKA. Taken together, it is suggested that the PKC-mediated phosphorylation is partly involved in AIKA.

• The Korean Journal of Physiology and Pharmacology
• /
• 제5권2호
• /
• pp.139-146
• /
• 2001

L-type $Ca^{2+}$ channels play an important role in regulating cytosolic $Ca^{2+}$ and thereby regulating hormone secretions in neuroendocrine cells. Since hormone secretions are also regulated by various kinds of protein kinases, we investigated the role of some kinase activators and inhibitors in the regulation of the L-type $Ca^{2+}$ channel currents in rat pituitary $GH_3$ cells using the patch-clamp technique. Phorbol 12,13-dibutyrate (PDBu), a protein kinase C (PKC) activator, and vanadate, a protein tyrosine phosphatase (PTP) inhibitor, increased the $Ba^{2+}$ current through the L-type $Ca^{2+}$ channels. In contrast, bisindolylmaleimide I (BIM I), a PKC inhibitor, and genistein, a protein tyrosine kinase (PTK) inhibitor, suppressed the $Ba^{2+}$ currents. Forskolin, an adenylate cyclase activator, and isobutyl methylxanthine (IBMX), a non-specific phosphodiesterase inhibitor, reduced $Ba^{2+}$ currents. The above results show that the L-type $Ca^{2+}$ channels are activated by PKC and PTK, and inhibited by elevation of cyclic nucleotides such as cAMP. From these results, it is suggested that the regulation of hormone secretion by various kinase activity in $GH_3$ cells may be attributable, at least in part, to their effect on L-type $Ca^{2+}$ channels.