检索结果-内蒙古大学图书馆

Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase

JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第52期274卷 37385-37390页

作者： Feng, JH Ito, M Ichikawa, K Isaka, N Nishikawa, M Hartshorne, DJ Nakano, T Mie Univ Sch Med Dept Internal Med 1 Tsu Mie 5148507 Japan Mie Univ Sch Med Dept Internal Med 2 Tsu Mie 5148507 Japan Univ Arizona Muscle Biol Grp Tucson AZ 85721 USA

It is clear from several studies that myosin phosphatase (MP) can be inhibited via a pathway that involves RhoA. However, the mechanism of inhibition is not established;These studies were carried out to test the hypothesis that Rho-kinase (Rho-associated kinase) via phosphorylation of the myosin phosphatase target subunit 1 (MYPT1) inhibited MP activity and to identify relevant sites of phosphorylation. Phosphorylation by Rho-kinase inhibited MP activity and this reflected a decrease in V-max. Activity of MP with different substrates also was inhibited by phosphorylation, Two major;sites of phosphorylation on MYPT1 were Thr(695) and Thr(850). Various point mutations were designed for these phosphorylation sites. Following thiophosphorylation by Rho kinase and assays of phosphatase activity it was determined that Thr(695) was responsible for inhibition. A site- and phosphorylation-specific antibody was developed for the sequence flanking Thr(695) and this recognized only phosphorylated Thr(695) in both native and recombinant MYPT1. Using this antibody it was shown that stimulation of serum-starved Swiss 3T3 cells by lysophosphatidic acid, thought to activate RhoA pathways, induced an increase in Thr(695) phosphorylation on MYPT1 and this effect was blocked by a Rho-kinase inhibitor, Y-27632. In summary, these results offer strong support for a physiological role of Rho-kinase in regulation of MP activity.

关键词： 3T3细胞酰胺类/药理学抗体特异性细胞内信号肽和蛋白质类溶血磷脂素类/药理学肌平滑/酶学诱变定点肌球蛋白轻链磷酸酶磷蛋白磷酸酶类/化学磷蛋白磷酸酶类/免疫学磷蛋白磷酸酶类/代谢磷酰化蛋白质丝氨酸苏氨酸激酶/生理学吡啶类/药理学苏氨酸 rho相关激酶类动物小鼠

来源：评论

学校读者我要写书评

暂无评论

Stimulation of p38 mitogen-activated protein kinase is an early regulatory event for the cadmium-induced apoptosis in human promonocytic cells

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第15期275卷 11418-11424页

作者： Galan, A Garcia-Bermejo, ML Troyano, A Vilaboa, NE de Blas, E Kazanietz, MG Aller, P CSIC Ctr Invest Biol E-28006 Madrid Spain Univ Penn Sch Med Ctr Expt Therapeut Philadelphia PA 19104 USA Univ Penn Sch Med Dept Pharmacol Philadelphia PA 19104 USA

Pulse treatment of U-937 promonocytic cells with cadmium chloride (2 h at 200 mu M) provoked apoptosis and induced a rapid phosphorylation of p38 mitogen-activated protein kinase (p38(MAPK)) as Well as a late phosphorylation of extracellular signal-regulated protein kinases (ERK1/2). However, although the p38(MAPK)-specific inhibitor SB203580 attenuated apoptosis, the process was not affected by the ERK-specific inhibitor PD98059. The attenuation of the cadmium-provoked apoptosis by SB203580 was a highly specific effect. In fact, the kinase inhibitor did not prevent the generation of apoptosis by heat shock and camptothecin, nor the generation of necrosis by cadmium treatment of glutathione-depleted cells, nor the cadmium-provoked activation of the stress response. The generation of apoptosis was preceded by intracellular H2O2 accumulation and was accompanied by the disruption of mitochondrial transmembrane potential, both of which were inhibited by SB203580, On the other hand, the antioxidant agent butylated hydroxyanisole-inhibited apoptosis but did not prevent p38(MAPK) phosphorylation. In a similar manner, p38(MAPK) phosphorylation was not affected by the caspase inhibitors Z-VAD and DEVD-CHO, which nevertheless prevented apoptosis. These results indicate that p38(MAPK) activation is an early and specific regulatory event for the cadmium-provoked apoptosis in promonocytic cells.

关键词：细胞凋亡/药物作用镉/毒性钙-钙调素依赖性蛋白激酶类/生理学半胱氨酸天冬氨酸蛋白酶/代谢酶激活类黄酮物质/药理学咪唑类/药理学膜电位线粒体/生理学丝裂原活化蛋白激酶1/生理学丝裂原活化蛋白激酶3 丝裂原激活蛋白激酶类/生理学坏死氧化性应激吡啶类/药理学 U937细胞 p38丝裂原活化蛋白激酶类人类

来源：评论

学校读者我要写书评

暂无评论

An inhibitor of p38 mitogen-activated protein kinase protects neonatal cardiac myocytes from ischemia

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第10期274卷 6272-6279页

作者： Mackay, K Mochly-Rosen, D Stanford Univ Sch Med Dept Mol Pharmacol Stanford CA 94305 USA

Cellular ischemia results in activation of a number of kinases, including p38 mitogen-activated protein kinase (MAPK);however, it is not yet clear whether p38 MAPK activation plays a role in cellular damage or is part of a protective response against ischemia, We have developed a model to study ischemia in cultured neonatal rat cardiac myocytes. In this model, two distinct phases of p38 MAPK activation were observed during ischemia. The first phase began within 10 min and lasted less than 1 h, and the second began after 2 h and lasted throughout the ischemic period. Similar to previous studies using in vivo models, the nonspecific activator of p38 MAPK and c-Jun NH2-terminal kinase, anisomycin, protected cardiac myocytes from ischemic injury, decreasing the release of cytosolic lactate dehydrogenase by approximately 25%. We demonstrated, however, that a selective inhibitor of p38 MAPK, SB 203580, also protected cardiac myocytes against extended ischemia in a dose-dependent manner. The protective effect was seen even when the inhibitor was present during only the second, sustained phase of p38 MAPK activation. We found that ischemia induced apoptosis in neonatal rat cardiac myocytes and that SE 203580 reduced activation of caspase-3, a key event in apoptosis. These results suggest that p38 MAPK induces apoptosis during ischemia in cardiac myocytes and that selective inhibition of p58 MAPK could be developed as a potential therapy for ischemic heart disease.

关键词：钙-钙调素依赖性蛋白激酶类/拮抗剂和抑制剂钙-钙调素依赖性蛋白激酶类/代谢酶抑制剂/药理学酶抑制剂/治疗应用心室/酶学心室/病理学咪唑类/药理学咪唑类/治疗应用丝裂原激活蛋白激酶类心肌缺血/酶学心肌缺血/预防和控制磷酰化吡啶类/药理学吡啶类/治疗应用大鼠 Sprague-Dawley p38丝裂原活化蛋白激酶类动物大鼠

来源：评论

学校读者我要写书评

暂无评论

The requirement of both extracellular regulated kinase and p38 mitogen-activated protein kinase for stimulation of cytosolic phospholipase A₂ activity by either FcγRIIA or FcγRIIIB in human neutrophils -: A possible role for Pyk2 but not for the Grb2-Sos-Shc complex

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第17期275卷 12416-12423页

作者： Hazan-Halevy, I Seger, R Levy, R Ben Gurion Univ Negev Fac Hlth Sci Dept Clin Biochem Infect Dis Lab IL-84105 Beer Sheva Israel Soroka Med Ctr IL-84105 Beer Sheva Israel Weizmann Inst Sci Dept Regulat Biol IL-76100 Rehovot Israel

The signal transduction pathways initiated by opsonized zymosan (OZ) leading to activation of cytosolic phospholipase A(2) (cPLA(2)) in human neutrophils remain obscure. In a previous study, we showed that the activation of cPLA(2) by OZ is tyrosine kinase-dependent. The present study demonstrates that the signals initiated by OZ involve activation of tyrosine kinase Pyk2 but not the formation of the adhesion protein complex, Shc-Grb2-Sos. Stimulation of cPLA(2) activity by OZ is mediated by Fc gamma receptors (Fc gamma Rs) and not by complement receptors for the C3b protein. Cross-linking of Fc gamma RILA or Fc gamma RIIIB induces p38 mitogen-activated protein (MAP) kinase and extracellular regulated kinase (ERK) phosphorylation. The kinetics of cPLA(2) activity stimulated by either of the Fc gamma Rs or by both is similar to that of p38 MAP kinase and was detected as early as 15 s after stimulation, maintained a plateau for 10 min, and decreased thereafter. ERK activation was detected also within 15 s but decreased significantly 5 min after stimulation. The MEK inhibitor, PD-098059, or the p38 MAP kinase inhibitor, SB-203580, caused a partial inhibition during the time course of cPLA(2) activity, whereas their combination caused a total inhibition. Thus, although ERK activation is significantly shorter than that of p38 MAP kinase, it is equally required for activation and maintenance of cPLA(2) activity by occupancy of a single receptor, Fc gamma RILA or Fc gamma RIIIB.

关键词：抗原 CD/生理学胞质溶胶/酶学酶激活酶抑制剂/药理学类黄酮物质/药理学咪唑类/药理学免疫印迹法丝裂原激活蛋白激酶类/拮抗剂和抑制剂丝裂原激活蛋白激酶类/生理学模型生物学中性白细胞/酶学磷脂酶A/代谢磷酰化蛋白质结合吡啶类/药理学受体 IgG/生理学信号传导超氧化物类/代谢时间因素酪氨酸/代谢酵母多糖/代谢 p38丝裂原活化蛋白激酶类人类

来源：评论

学校读者我要写书评

暂无评论

Apoptosis signal-regulating kinase 1 (ASK1) induces neuronal differentiation and survival of PC12 cells

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第13期275卷 9805-9813页

作者： Takeda, K Hatai, T Hamazaki, TS Nishitoh, H Saitoh, M Ichijo, H Tokyo Med & Dent Univ Dept Biomat Sci Fac Dent Bunkyo Ku Tokyo 1138549 Japan

Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase kinase kinase that activates the c-dun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase signaling cascades, We report here that expression of constitutively active ASK1 (ASK1 Delta N) induces neurite outgrowth in the rat pheochromocytoma cell line PC12, We found that p38 and to a lesser extent JNK, but not ERK, were activated by the expression of ASK1 Delta N in PC12 cells. ASK1 Delta N-induced neurite outgrowth was strongly inhibited by treatment with the p38 inhibitor SB203580 but not with the MEK inhibitors, suggesting that activation of p38, rather than of ERK, is required for the neurite-inducing activity of ASK1 in PC12 cells. We also observed that ASK1 Delta N induced expression of several neuron-specific proteins and phosphorylation of neurofilament proteins, confirming that PC12 cells differentiated into mature neuronal cells by ASK1. Moreover, ASK1 Delta N-expressing PC12 cells survived in serum-starved condition. ASK1 thus appears to mediate signals leading to both differentiation and survival of PC12 cells. Together with previous reports indicating that ASI(1 functions as a pro-apoptotic signaling intermediate, these results suggest that ASK1 has a broad range of biological activities depending on cell types and/or cellular context.

关键词：拟南芥蛋白质类钙-钙调素依赖性蛋白激酶类/拮抗剂和抑制剂钙-钙调素依赖性蛋白激酶类/代谢细胞分化/生理学细胞存活/生理学培养基无血清酶激活酶抑制剂/药理学咪唑类/药理学丝裂原激活蛋白激酶类神经突神经元/细胞学 PC12细胞植物蛋白质类/生理学吡啶类/药理学 p38丝裂原活化蛋白激酶类动物大鼠

来源：评论

学校读者我要写书评

暂无评论

p38 mitogen-activated protein kinase negatively regulates the induction of phase II drug-metabolizing enzymes that detoxify carcinogens

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第4期275卷 2322-2327页

作者： Yu, R Mandlekar, S Lei, W Fahl, WE Tan, TH Kong, ANT Univ Illinois Dept Pharmaceut & Phamacodynam Ctr Pharmaceut Biotechnol Coll Pharm Chicago IL 60612 USA Univ Wisconsin Mcardle Lab Canc Res Madison WI 53706 USA Baylor Coll Med Dept Microbiol & Immunol Houston TX 77030 USA

Phase II drug-metabolizing enzymes, such as glutathione S-transferase and quinone reductase, play an important role in the detoxification of chemical carcinogens. The induction of these detoxifying enzymes by a variety of agents occurs at the transcriptional level and is regulated bg a cis-acting element, called the antioxidant response element (ARE) or electrophile-response element. In this study, we identified a signaling kinase pathway that negatively regulates ARE-mediated gene expression. Treatment of human hepatoma HepG2 and murine hepatoma Hepalclc7 cells with tert-butylhydroquinone (tBHQ) stimulated the activity of p38, a member of mitogen-activated protein kinase family. Inhibition of p38 activation by its inhibitor, SB203580, enhanced the induction of quinone reductase activity and the activation of ARE reporter gene by tBHQ. In contrast, SB202474, a negative analog of SB203580, had little effect. Consistent with this result, interfering with the p38 kinase pathway by overexpression of a dominant-negative mutant of p38 or MKK3, an immediate upstream regulator of p38, potentiated the activation of the ARE reporter gene by tBHQ, whereas the wild types of p38 and MKK3 diminished such activation. In addition, inhibition of p38 activity augmented the induction of ARE reporter gene activity by tert-butylhydroxyanisole, sulforaphane, and p-naphthoflavone. Thus, p38 kinase pathway functions as a negative regulator in the ARE-mediated induction of phase II detoxifying enzymes.

关键词：抗氧化剂/代谢丁羟茴香醚/药理学致癌物/药代动力学酶激活酶诱导基因表达调控酶学基因报告氢醌类/药理学咪唑类/药理学异硫氰酸盐类动力学 MAP激酶激酶3 丝裂原激活蛋白激酶激酶类/代谢丝裂原激活蛋白激酶类/代谢 NAD(P)H脱氢酶(醌)/生物合成蛋白酪氨酸激酶类/代谢吡啶类/药理学硫氰酸盐类/药理学肿瘤细胞培养的 β萘黄酮/药理学 p38丝裂原活化蛋白激酶类动物人类小鼠

来源：评论

学校读者我要写书评

暂无评论

Detection of glucagon-dependent GTPγS binding in high-throughput format

引用

ANALYTICAL BIOCHEMISTRY 2002年第1期301卷 156-159页

作者： Dallas-Yang, Q Qureshi, SA Xie, D Zhang, BB Jiang, GQ Merck Res Labs Dept Mol Endocrinol Rahway NJ 07065 USA

来源：评论

学校读者我要写书评

暂无评论

Inhibition of IκB kinase activity by sodium salicylate in vitro does not reflect its inhibitory mechanism in intact cells

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第15期275卷 10925-10929页

作者： Alpert, D Vilcek, J NYU Sch Med Dept Microbiol New York NY 10016 USA

Sodium salicylate inhibits activation of the transcription factor NF-kappa B by blocking the phosphorylation and degradation of the NF-kappa B inhibitor I kappa B alpha. We previously demonstrated that salicylate inhibits I kappa B alpha degradation induced by tumor necrosis factor (TNF) but not by interleukin-1 (IL-1) and implicated p38 mitogen-activated protein kinase activation by salicylate in the inhibition of TNF-induced I kappa B alpha phosphorylation. Both TNF and IL-1 rapidly activate the I kappa B kinase (IKK) complex, containing the catalytic subunits IKK alpha and IKK beta, which directly phosphorylates I kappa B proteins. Others have recently suggested that salicylate inhibits NF-kappa B activation by directly binding to IKK beta. To clarify the mechanism whereby salicylate inhibits IKK activity, we examined its effects upon cytokine-induced IKK activity in intact cells and in vitro, Treatment of intact cells with salicylate inhibited TNF-induced but not IL-1-induced IKK activity, and this inhibition was prevented by the p38 inhibitor SB203580. In contrast, inhibition of IKK activity by salicylate in vitro was neither selective for TNF nor affected by SB203580. In vitro, salicylate treatment comparably inhibited the kinase activity of overexpressed IKK alpha and IKK beta and also decreased p38 kinase activity. Therefore, direct inhibition of IRK activity in vitro does not reflect the inhibitory mechanism of salicylate in intact cells, which involves interference with TNF signaling.

关键词： COS细胞钙-钙调素依赖性蛋白激酶类/拮抗剂和抑制剂 I-κB蛋白质类/拮抗剂和抑制剂咪唑类/药理学白细胞介素1/药理学丝裂原激活蛋白激酶类吡啶类/药理学水杨酸钠/药理学肿瘤坏死因子α/药理学 p38丝裂原活化蛋白激酶类动物人类

来源：评论

学校读者我要写书评

暂无评论

The preclinical pharmacological profile of WAY-132983, a potent M1 preferring agonist

引用

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第2期292卷 584-596页

作者： Bartolomeo, AC Morris, H Buccafusco, JJ Kille, N Rosenzweig-Lipson, S Husbands, MG Sabb, AL Abou-Gharbia, M Moyer, JA Boast, CA Wyeth Ayerst Res CNS Disorders Div Cent Nervous Syst Med Chem Cent Nervous Syst Res Princeton NJ 08543 USA Med Coll Georgia Dept Pharmacol & Toxicol Alzheimers Res Ctr Augusta GA 30912 USA Vet Adm Med Ctr Augusta GA 30904 USA

Muscarinic M1 preferring agonists may improve cognitive deficits associated with Alzheimer's disease. Side effect assessment of the M1 preferring agonist WAY-132983 showed significant salivation (10 mg/kg i.p. or p.o.) and produced dose-dependent hypothermia after i.p. or p.o. administration. WAY-132983 significantly reduced scopolamine (0.3 mg/kg i.p.) induced hyperswimming in mice. Cognitive assessment in rats used pretrained animals in a forced choice, 1-h delayed non-match-to-sample radial arm maze task. WAY-132983 (0.3 mg/kg i.p) significantly reduced scopolamine (0.3 mg/kg s.c.)-induced errors. Oral WAY-132983 attenuated scopolamine-induced errors;that is, errors produced after combining scopolamine and WAY-132983 (to 3 mg/kg p.o.) were not significantly increased compared with those of vehicle-treated control animals, whereas errors after scopolamine were significantly higher than those of control animals. With the use of miniosmotic pumps, 0.03 mg/kg/day (s.c.) WAY-132983 significantly reduced AF64A (3 nmol/3ml/lateral ventricle)-induced errors. Verification of AF64A cholinotoxicity showed significantly lower choline acetyltransferase activity in the hippocampi of AF64A-treated animals, with no significant changes in the striatal or frontal cortex. Cognitive assessment in primates involved the use of pretrained aged animals in a visual delayed match-to-sample procedure. Oral WAY-132983 significantly increased the number of correct responses during short and long delay interval testing. These effects were also apparent 24 h after administration. WAY-132983 exhibited cognitive benefit at doses lower than those producing undesirable effects;therefore, WAY-132983 is a potential candidate for improving the cognitive status of patients with Alzheimer's disease.

关键词：氮丙啶类/药理学行为动物/药物作用脑/代谢桥基化合物/投药和剂量桥基化合物/药理学桥基化合物/毒性胆碱/类似物和衍生物胆碱/药理学胆碱O-乙酰转移酶/代谢认知/药物作用剂量效应关系药物药物相互作用额叶/药物作用额叶/代谢海马/代谢低温/化学诱导恒河猴毒蕈碱激动剂/投药和剂量毒蕈碱激动剂/药理学毒蕈碱激动剂/毒性神经肌肉阻滞药/药理学吡嗪类/投药和剂量吡嗪类/药理学吡嗪类/毒性吡啶类/药理学大鼠 Sprague-Dawley 唾液分泌/药物作用东莨菪碱/药理学噻二唑类/药理学时间因素视皮质/药物作用视皮质/代谢动物女(雌)性男(雄)性小鼠大鼠

来源：评论

学校读者我要写书评

暂无评论

Reversal of antipsychotic-induced working memory deficits by short-term doper D1 receptor stimulation

引用

SCIENCE 2000年第5460期287卷 2020-2022页

作者： Castner, SA Williams, GV Goldman-Rakic, PS Yale Univ Sch Med Neurobiol Sect New Haven CT 06510 USA

Chronic blockade of dopamine D2 receptors, a common mechanism of action for antipsychotic drugs, down-regulates D1 receptors in the prefrontal cortex and, as shown here, produces severe impairments in working memory. These deficits were reversed in monkeys by short-term coadministration of a D1 agonist, ABT 431, and this improvement was sustained for more than a year after cessation of D1 treatment. These findings indicate that pharmacological modulation of the D1 signaling pathway can produce long-lasting changes in functional circuits underlying working memory. Resetting this pathway by brief exposure to the agonist may provide a valuable strategy for therapeutic intervention in schizophrenia and other dopamine dysfunctional states.

关键词：抗精神病药/药理学环AMP/代谢多巴胺/代谢多巴胺激动剂/药理学多巴胺拮抗剂/药理学减量调节氟哌啶醇/药理学直鼻猴亚目记忆/药物作用额叶前皮质/药物作用额叶前皮质/代谢精神运动性行为/药物作用吡啶类/药理学受体多巴胺D1/激动剂受体多巴胺D1/代谢信号传导四氢萘类/药理学时间因素动物女(雌)性

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：