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酪氨酸蛋白激酶

酪氨酸蛋白激酶的相关文献在1992年到2022年内共计224篇,主要集中在肿瘤学、药学、基础医学 等领域,其中期刊论文159篇、会议论文8篇、专利文献140558篇;相关期刊117种,包括生物化学与生物物理学报:英文版、中华肝脏病杂志、中华实验外科杂志等; 相关会议8种,包括2006全国大肠癌转移与复发诊治学习班暨第八届广东省大肠癌学术研讨会、第七次全国呼吸病学术会议、第九届华东地区实验动物科学学术交流会等;酪氨酸蛋白激酶的相关文献由584位作者贡献,包括舒永志、许霖水、孙黎光等。

酪氨酸蛋白激酶—发文量

期刊论文>

论文:159 占比:0.11%

会议论文>

论文:8 占比:0.01%

专利文献>

论文:140558 占比:99.88%

总计:140725篇

酪氨酸蛋白激酶—发文趋势图

酪氨酸蛋白激酶

-研究学者

  • 舒永志
  • 许霖水
  • 孙黎光
  • Y·娄
  • 刘小菁
  • 张劲松
  • 杨江苏
  • 王一平
  • 王占科
  • 王琼
  • 期刊论文
  • 会议论文
  • 专利文献

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    • 王皓; 涂峰; 赵文斌; 张麟
    • 摘要: 目的研究通阳中药葱白提取物(AYMOE)对低压低氧诱导的血小板激活和促凝状态的影响。方法将42只成年雄性SD大鼠随机分为对照组(暴露于常压常氧环境)、低压低氧组(Hyp组,暴露于低压低氧环境)、Hyp+AYMOE-100组(暴露于低压低氧环境并口服AYMOE 100 mg/kg)、Hyp+AYMOE-200组(暴露于低压低氧环境并口服AYMOE 200 mg/kg)、Hyp+AYMOE-300组(暴露于低压低氧环境并口服AYMOE 300 mg/kg)、Hyp+anti-CD42c组(暴露于低压低氧环境并尾静脉注射antiCD42c 5 mg/kg)、Hyp+AYMOE-200+rh Lyn组[暴露于低压低氧环境并口服AYMOE 200 mg/kg联合尾静脉注射重组人酪氨酸蛋白激酶Lyn(rh Lyn) 4.8 mg/kg],每组6只。低压低氧暴露7 d后,ELISA检测各组大鼠血清血栓素A2(TXA2)以及血小板激活因子(PAF)含量,检测大鼠血小板的凝集率,HE染色观察大鼠肺组织病理变化,Western blot检测GPIb-Ⅸ-Ⅴ、Lyn、磷酸化的Lyn(p-Lyn)的表达。结果与对照组比较,暴露于低压低氧的各组大鼠血清TXA2、PAF水平及血小板凝集率升高,GPIb-Ⅸ-Ⅴ、Lyn、p-Lyn蛋白表达上调(P <0.05)。与Hyp组相比,Hyp+AYMOE-100组、Hyp+AYMOE-200组、Hyp+AYMOE-300组的血小板凝集率、血清TXA2、PAF的水平降低,差异均有统计学意义(P <0.05),其中以Hyp+AYMOE-200组抑制效果最明显(P <0.05)。与对照组比较,Hyp组大鼠因低氧而发生血管堵塞,肺静脉血管腔空间狭小;与Hyp组相比,Hyp+AYMOE-200组大鼠肺静脉血管栓塞明显缓解。与Hyp组相比,Hyp+anti-CD42c组和Hyp+AYMOE-200组GPIb-Ⅸ-Ⅴ、Lyn、p-Lyn蛋白表达下调,差异均有统计学意义(P <0.05)。与Hyp+AYMOE-200组比较,Hyp+AYMOE-200+rh Lyn组血小板凝集率、血清TXA2和PAF水平均较高,Lyn和p-Lyn蛋白表达均增加,差异均有统计学意义(P <0.05)。结论 AYMOE可通过抑制GPIb-Ⅸ-Ⅴ和Lyn减少低压低氧诱导的血小板激活并改善促凝状态。
    • 陈腾祥; 梁黎; 曾智锐; 雷珊; 王婧雅; 孙远梅; 兰金芝; 薛燕
    • 摘要: 目的:研究五味子甲素对人鼻咽癌细胞HONE-1增殖、迁移和侵袭的影响及其可能机制.方法:以HONE-1细胞为研究模型,使用不同浓度[0(空白对照)、10、20、40μmol/L]的五味子甲素处理后,分别采用CCK-8试验、划痕试验和Transwell小室试验检测细胞的增殖、迁移和侵袭能力变化;通过计算机分子对接分析五味子甲素与酪氨酸蛋白激酶(Met)蛋白的结合能力;采用Western blotting法检测细胞中磷酸化酪氨酸蛋白激酶(p-Met)、磷酸化磷脂酰肌醇-3-激酶(p-PI3K)、磷酸化蛋白激酶B(p-Akt)、B淋巴细胞瘤2(Bcl-2)和N-钙黏蛋白(N-cadherin)的相对表达量.结果:与空白对照比较,10、20、40μmol/L五味子甲素处理后细胞的增殖、迁移和侵袭能力均显著减弱(P<0.05);分子对接结果显示,五味子甲素能与Met蛋白的活性口袋稳定结合;Western blot-ting试验结果显示,与空白对照比较,10、20、40μmol/L五味子甲素处理后细胞中p-Met、p-PI3K、p-Akt、Bcl-2和N-cadherin蛋白的相对表达量均显著降低(P<0.05).结论:五味子甲素可通过抑制Met/PI3K/Akt信号通路的活化来抑制HONE-1细胞的增殖、迁移和侵袭.
    • 汪治宇; 郭盛虎; 李幸; 曹静; 王聪; 韩雪
    • 摘要: 目的 研究芍药总苷对6MV-X射线放射性食管炎模型大鼠的影响.方法 取健康雄性Wistar大鼠,用6MV-X射线单次照射建立放射性食管炎模型,空白组大鼠17只不接受射线照射.按照体重将造模成功大鼠随机分为4组,每组17只:模型组、对照组和低、高2个剂量实验组.模型组和空白组给予0.9% NaCl 2 mL,tid;对照组给予西药合剂(0.9% NaCl 250 mL+利多卡因3.2mL+地塞米松1.6 mg+硫酸庆大霉素5.12万单位)2 mL tid;低、高2个剂量实验组分别给予2,6 mg·mL-芍药总苷溶液2 mL,tid,均连续给药8d.用光学显微镜观察食管组织病理变化并评分,用酶联免疫吸附法测定血清Ⅲ型前胶原(PC Ⅲ)、转化生长因子β1(TGF-β1)水平,用蛋白质免疫印迹法检测食管组织神经生长因子(NGF)、酪氨酸蛋白激酶A(TrkA)蛋白、P75蛋白表达水平.结果 给药后,空白组、模型组、对照组和低、高2个剂量实验组食管组织病理变化程度评分分别为0,(4.24±0.58),(2.15±0.26),(1.08±0.15),(0.53±0.07)分,这5组的血清PC Ⅲ水平分别为(40.73±5.24),(90.48±10.38),(71.23±8.72),(58.46±7.66),(49.36±6.12) μg·L-1,这5组的食管组织NGF蛋白表达水平分别为0.54±0.07,1.32±0.18,1.13±0.12,0.84 ±0.11,0.69±0.08,组间比较差异均有统计学意义(均P<0.05).结论 芍药总苷能够减轻6MV-X射线放射性食管炎模型大鼠的病理损伤程度,降低血清PCⅢ、TGF-β1水平,防治食管纤维化,其作用可能与降低NGF及其受体TrkA蛋白和P75蛋白的表达水平有关.%Objective To analyze the effect of total glucosides of peony (TGP) on nerve growth factor(NGF) and its receptor in 6MV-X ray radiation induced esophagitis model rats.Methods The male Wistar rats were selected,and radiation esophagitis rat model were established by 6MV-X ray single irradiation,the model rats were randomly divided into model group,control group,experimental-L group,experimental-H group,each with 17 rats;another 17 rats in blank group did not receive radiation.The model group and blank group were treated with sodium chloride injection 2 mL,tid;the control group was treated with western medicine mixture (sodium chloride injection 250 mL + lidocaine 3.2 mL + dexamethasone 1.6 mg + gentamicin sulphate 51.2 × 104 u) 2 mL,tid;the experimental-L group and experimental-H group were treated with 2,6 mg · mL-1 TGP solution 2 mL,tid.All rats were given the drug continuously for 8 days.The score of pathological changes of esophagus were observed by optical microscope.The serum levels of type Ⅲ procollagen (PC Ⅲ) and transforming growth factor β1 (TGF-β1) were detected by enzyme-linked immunosorbent assay.The expression levels of nerve growth factor(NGF),tyrosine protein kinase A (TrkA)protein,P75 protein were detected by Western blotting.Results After treatment,the score of pathological changes of esophagus in blank group,model group,corntrol group,experimental-L group,experimental-H group were respectively 0,(4.24 ± 0.58),(2.15 ± 0.26),(1.08 ± 0.15) and (0.53 ± 0.07) point,serum PC Ⅲ levels in the 5 groups were respectively (40.73 ± 5.24),(90.48 ± 10.38),(71.23 ± 8.72),(58.46 ± 7.66) and (49.36-± 6.12) μg · L-1,the expression levels of NGF in esophageal tissue in the 5 groups were respectively 0.54 ± 0.07,1.32 ± 0.18,1.13 ± 0.12,0.84 ± 0.11 and 0.69 ± 0.08,there were significant differences between groups (all P < 0.05).Conclusion TGP can reduce the pathological damage degree of 6MV-X ray radiation induced esophagitis model rats,reduce serum PC Ⅲ and TGF-β1 levels,prevent and cure esophageal fibrosis,which may be related to decrease the expression levels of NGF and its receptor TrkA protein and P75 protein.
    • 陈少军; 董珂; 陈宏降
    • 摘要: 丹酚酸A是中药丹参中一种水溶性酚酸类化合物,具有较强的抗氧化性,发挥着多种药理作用.但其作用靶点仍需要进一步阐释.本文以SwissTargetPredicition在线服务器为工具,以SAA为研究对象,采用化学相似性搜索其作用靶点.实验结果显示Fyn、Src等Src酪氨酸家族蛋白是SAA作用的潜在靶点,正向分子对接也显示了SAA与Fyn的核心氨基酸有相互作用.综上,Fyn、Src等Src酪氨酸激酶家族蛋白可能是SAA的潜在靶蛋白之一.%Salvianolic acid A (SAA) is a water-soluble component from Danshen.It plays many pharmacological roles in many diseases treatments with its potentialantioxidant activity.But its targets is still need to be illustrated.In this study,SwissTargetPrediction server was used to identify the potential targets of SAA by chemical similarity searching.The results showed that Src tyrosine family protein,such as Fyn and Src,may be the targets of SAA.Moreover,docking results showed SAA can interact with key residues of Fyn.In conclusion,Src tyrosine family protein,such as Fyn and Src,may be the potential targets of SAA.
    • 陈浩; 李七一; 陆曙
    • 摘要: 酪氨酸蛋白激酶/信号转导因子和转录激活因子(JAK/STAT)通路是一条由细胞因子刺激的信号转导通路,参与细胞的增殖、分化、凋亡以及免疫调节等许多重要的生物学过程。细胞因子信号转导抑制因子(SOCS)家族是该通路最重要的抑制信号因子。本文就中医药在调控 JAK/STAT、SOCS信号通路的研究做一综述。
    • 白倩; 杨现会; 付红光; 孙凯
    • 摘要: Objective To study the protective effects of penehyclidine hydrochloride (HPC) on myocardial ischemia-reperfusion injury (IRI),and investigated if this effrcts through janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) pathways.Methods 36 healthy male SD rats were divided into 6 groups:(1) Sham-operated group (Sham),(2) ischemia-reperfusion groups (IRI),(3) penehyclidine hydrochloride treated group (PHC),(4) Group of penehyclidine hydrochloride in +AG-490 (PHC +AG),(5) AG-490 Group (AG),(6) Dmethyl sulfoxide (DMSO) Group.Sham groups:left anterior descending (LAD) coronary artery was threaded bot the coronary artery was not blocked;IRI group:LAD ligation 30 min and 120 minutes reperfusion;PHC and PHC + AG groups:30 min before ischemia,intraperitoneal injection of PHC (2 mg/kg) then remaining the same strategy with IRI group;PHC + AG group,AG group and the DMSO group:10 minutes before reperfusion intravenous JAK2 inhibitor AG-490 (3 mg/kg) and 1% in DMSO solution (0.4 ml/kg) respectively,and the rest was same with IRI group.Monitors continuously monitored and recorded the basis of heart rate (HR),mean arterial pressure (MAP) and rate-pressure product (RPP) before ischemia,and 30 min,60 min,90 min after reperfusion.After 90 min reperfusion,Rats were killed in each group,removed the left ventricular myocardium,extracted the total protein,useing Western blotting method to analyze the expression of JAK2 and STAT3 protein and phosphorylation of JAK2 (p-JAK2) and phosphorylation of STAT3 (p-STAT3).Results Compared with the basis of HR,MAP,and RPP before ischemia in each group (IRI groups,PHC group,PHC +AG group,AG and DMSO group),HR [(343 ±20) bmp],MAP [(109 ±11) mmHg (1 mmHg =0.133 kPa)] and RPP (44 ±3),after the reperfusion:HR [(280 ± 12) bmp],MAP [(84 ± 15) mmHg] and RPP (29 ±5) reduced (P<0.05);Compared with the IRI groups after the reperfusion,HR [(320 ± 15) bmp],MAP [(90 ± 11) mmHg] and RPP (34 ±6) in PHC group increased (P < 0.05);Compared with the PHC groups after the reperfusion,HR [(301 ± 14) bmp],MAP [(83 ±11) mmHg] and RPP (29 ±4) in PHC +AG group declined (P<0.05).Analysis result of the protein Gray value of p-JAK2/JAK2,p-STAT3/STAT3 in myocardial shows:Compared with the IRI groups (0.50 ±0.08,0.30 ±0.09),the value in PHC group (0.91 ±0.02,0.65 ± 0.05) increased (P <0.01);Compared with the PHC groups,the value in PHC + AG group (0.28 ± 0.04,0.25 ± 0.08) declined (P < 0.01).Conclusion PHC pretreatment can activate JAK/STAT signal transduction pathway play a protective role in myocardial ischemia-reperfusion.JAK/STAT signal transduction inhibitor AG-490 can decline the myocardial ischemia-reperfusion protective effect of PHC preconditioning.%目的 观察盐酸戊乙奎醚(HPC)对缺血再灌注心肌的保护作用,探讨HPC通过调控酪氨酸蛋白激酶2/信号转导子和转录激活子3(JAK2/STAT3)通路发挥抗心肌缺血再灌注损伤(IRI)作用.方法 36只健康雄性大鼠随机分为6组:(1)假手术组(Sham);(2)缺血再灌注组(IRI);(3)盐酸戊乙奎醚处理组(PHC);(4)盐酸戊乙奎醚处理+ AG-490组(PHC+AG);(5)AG-490组(AG);(6)二甲基亚砜组(DMSO).Sham组:左冠状动脉前降支(LAD)穿线并不阻断冠状动脉;IRI组:结扎LAD 30 min、再灌注120 min;PHC组和PHC+ AG组在缺血处理前30 min,经腹腔注射PHC(2 mg/kg),其余同IRI组;PHC+ AG组、AG组和DMSO组在再灌前10 min分别静脉注射JAK2抑制剂AG-490(3 mg/kg)及1%DMSO溶液(0.4mL/kg),其余同IRI组.用监护仪连续监测并记录缺血前纪录基础值、再灌后30、60、90 min记录心率(HR)、平均动脉压(MAP)和心率与收缩压的乘积(RPP).各组大鼠于再灌注开始90 min后处死,取出左心室心肌组织,提取总蛋白,用Western blot法分析心肌JAK2、STAT3和磷酸化JAK2(p-JAK2)、磷酸化STAT3(p-STAT3)的蛋白表达变化.结果 IRI组、PHC组、PHC+ AG组、AG组和DMSO组各组与组内缺血前基础值HR[(343±20)次/分]、MAP[(109±11) mmHg(1 mmHg=0.133 kPa)]和RPP (44 ±3)比较,再灌后HR[(280 ±12)次/分]、MAP[(84±15) mmHg]和RPP(29±5)降低(P<0.05);与灌注后IRI组比较,PHC组HR[(320±15)次/分]、MAP[(90±11) mmHg]和RPP(34±6)增高(P<0.05);与灌注后PHC组比较,PHC+ AG组HR[(301±14)次/分]、MAP[(83±11) mmHg]和RPP(29 ±4)降低(P<0.05).心肌p-JAK2/JAK2、p-STAT3/STAT3的蛋白灰度分析显示:与IRI组(0.50±0.08、0.30 ±0.09)比较,PHC组蛋白表达(0.91 ±0.02、0.65±0.05)增高(P<0.01);与PHC组比较,PHC+ AG组蛋白表达(0.28 ±0.04、0.25±0.08)降低(P<0.01).结论 PHC预处理可激活JAK/STAT信号转导通路发挥心肌保护作用.应用JAK/STAT信号转导通路抑制剂AG-490可使PHC缺血预处理丧失心肌保护作用.
    • 殷缘; 张天泰; 张大永
    • 摘要: JAK-3激酶(Janus kinase 3)作为酪氨酸蛋白激酶家族成员,在JAK-STAT (Janus kinase-signal transducer and activator of transcription)信号通路中起着非常重要的作用,研究证实JAK-3活性的调控在多种疾病的治疗中起着关键作用,针对该激酶的抑制剂已经有许多相关研究,并有多个JAK-3激酶抑制剂进入临床研究,表现出很好的JAK-3选择性和抑制活性,其中tofacitinib等抑制剂已经通过临床试验,被批准用于类风湿性关节炎的治疗.很多JAK-3抑制剂表现出良好抑制活性的同时,伴有一定的不良反应,有待于改进.本文综述了JAK-3激酶的结构功能以及JAK-3激酶抑制剂的研究进展,为后续研究提供参考.
    • 杨照环; 何笑冬; 王颖; 李倩; 舒小镭
    • 摘要: Objective In order to research the effect of tyrosine kinase inhibitor in combination with radiotherapy on the inhibi‐tion of breast cancer cells and breast cancer bearing nude mice .Methods Methyl thiazolyl tetrazolium (MTT) assay was used to e‐valuate the inhibition of different concentrations of TKI on breast cancer cells ,the breast cancer cells was divided into three groups :the TKI treatment group ,the cells in the control group (no the TKI processing) and the control group (non‐TKI and X‐ray irradia‐tion group) .The sensitivity of the cells in each group to X‐ray was compared by colony formation assay .MCF7 cells were xenograf‐ted in athymic nude mice to establish the animal model ,which was used to evaluate the effect of anti‐cancer .Results Colony form‐ing test showed that the separated use of any concentrations of the TKI inhibitor could inhibit the breast cells ,and the cell viability was significantly reduced;TKI combined with X‐ray irradiation could significantly increase the sensitivity of breast cancer cells to radiation ,and the difference was statistically significant(P<0 .05) .Compared to TKI inhibitor or X‐ray irradiation alone ,the combi‐nation of TKI inhibitor with X‐ray irradiation could inhibit the growth of tumor effectively .Conclusion The TKI inhibitor in com‐bination with radiotherapy can effectively inhibit the growth of breast cancer cells ,which provides a new theoretical basis for the im‐plementation of the clinical breast cancer radio sensitization .%目的:研究酪氨酸蛋白激酶抑制剂(TKI)联合放疗对乳腺癌细胞增殖及肿瘤生长的影响。方法利用噻唑蓝(MTT)实验检测不同浓度的TKI对乳腺癌细胞MCF‐7的抑制作用。将乳腺癌细胞分为生理盐水组,TKI干预组(TKI处理后无X射线照射),X射线干预组(X射线照射,无TKI处理)和TKI联合放疗干预组。利用克隆形成实验比较各组细胞存活率。构建乳腺癌裸鼠异位瘤模型,考察不同干预组对肿瘤生长的抑制能力。结果克隆形成实验显示,单独利用X射线照射或者单独利用任何浓度的TKI抑制剂处理乳腺癌细胞,细胞的存活率均较处理前出现降低;但TKI联合放疗乳腺癌细胞存活率较前面两组(TKI干预组,X射线干预组)差异有统计学意义(P<0.05)。与TKI预处理组或X射线干预组比较,TKI联合放疗干预组能够明显抑制荷瘤裸鼠肿瘤体积的增长,差异有统计学意义(P<0.05)。结论TKI抑制剂联合放疗可有效抑制乳腺癌细胞的生长。
    • 游锦梅; 许雅鑫; 吴彬; Yang Yong; 李钰; 陈显久
    • 摘要: 目的 以3种不同癌变程度的口腔细胞为工具,观察在干扰素α(IFN-α)作用下,JAK-信号转导子和转录激活子(STAT)-细胞因子信号抑制因子(SOCS)信号分子的表达变化,为深入理解口腔鳞状细胞癌(OSCC)细胞免疫逃逸的机制提供研究基础.方法 常规培养NOK、DOK、KB细胞.空白组加入完全培养液,二甲基亚砜(DMSO)对照组加入含有0.1% DMSO的完全培养液,实验组设10、100、500U/ml三个不同浓度组,每孔分别加入含不同浓度IFN-α的完全培养液,JAK抑制剂干预组在加入IFN-α前1h加入JAK抑制剂CP-690550 100 μmol/L.细胞培养24 h后检测.进行反转录聚合酶链反应(RT-PCR)和Western blot实验.结果 采用RT-PCR法检测显示:JAK1和JAK2在NOK细胞均有少量表达,IFN-α和CP-690550对NOK细胞组的JAK1和JAK2表达无影响,差异无统计学意义(P>0.05).100和500 U/ml的IFN-α能刺激DOK和KB细胞的JAK1和JAK2表达增加,差异均具有统计学意义(P<0.05).CP-690550能有效减低DOK和KB细胞的JAK1表达,差异均具有统计学意义(P<0.05),而对JAK2表达无作用.采用Western blot法检测显示:STAT1、STAT3和pSTAT3(Tyr705)在对照组均有表达,pSTAT1(Tyr701)在对照组无表达;IFN-α和CP-690550对NOK细胞组的STAT1、STAT3和pSTAT3(Tyr705)表达无影响,差异无统计学意义(P>0.05).100、500 U/ml的IFN-α能刺激DOK和KB细胞的pSTAT3(Tyr705)表达增加,差异均具有统计学意义(P<0.05);而对pSTAT1(Tyr701)的表达无影响.CP-690550能有效减低DOK和KB细胞的pSTAT3(Tyr705)表达,差异均具有统计学意义(P<0.05).采用Western blot法检测显示,SOCS1和SOCS3在对照组均有表达;IFN-α和CP-690550对NOK细胞组的SOCS1和SOCS3表达无影响,差异无统计学意义(P>0.05).100 U/ml和500 U/ml的IFN-α能刺激DOK和KB细胞的SOCS1表达增加,差异均具有统计学意义(P<0.05);而对SOCS3的表达无影响.CP-690550能有效减低DOK和KB细胞的SOCS1表达,差异均具有统计学意义(P<0.05).结论 IFN-α激活DOK和KB细胞JAK1和JAK2的表达,以JAK1激活为主;IFN-α通过激活DOK和KB细胞JAK1和JAK2的表达促进STAT3在Tyr705位点磷酸化;IFN-α通过促进STAT3磷酸化进一步促进SOCS1的表达,发挥对IFN-α作用的抑制作用,减少细胞凋亡.%Objective To observe the change of JAK-STAT-SOCS signal molecules after interferons alpha acting on the cancerous oral cells in 3 different degrees,namely NOK,DOK and KB cells,and to provide research foundation for the deep understanding of OSCC (oral squamous cell cancer) tumor ceils immune escape mechanism.Methods NOK,DOK,and KB cells were all cultured respectively,and then the third passage cells in the logarithmic growth phase were inoculated in cell culture plate.Blank control group of each hole was added 2 ml complete medium containing 10 % FPS.DMSO control group of each hole was added 2 ml complete medium containing 0.1% DMSO.And in experimental groups containing 10 U/ml,100 U/ml,and 500 U/ml interferons,complete culture medium were added to each hole containing different concentrations of interferons alpha.CP-690550 (100 μmol/L) was added before interferons alpha was added 1 h.All were detected by RT-PCR test and Western blot test after conventional cultured for 24 h.Results RT-PCR detection showed that JAK1 and JAK2 in NOK cells had a small amount of expression,interferons alpha and CP-690550 cells could not influence the expression of JAK1 and JAK2 of NOK group,and there was no statistically significant difference (P > 0.05).Interferons alpha in 100 and 500 U/ml could stimulate the increase of JAK1 and JAK2 expression in DOK and KB cells,and the differences were statistically significant (P < 0.05).CP-690550 could effectively reduce the JAK1 expression of DOK and KB cells,while had no effect on the expression of JAK2,and the differences were statistically significant (P < 0.05).Western blot showed that STAT1,STAT3 and pSTAT3 (Tyr705) all expressed in the control group,while pSTAT1 (Tyr701) didn't express in the control group.Interferons alpha and CP-690550 cells had no effect on STAT1,STAT3 and pSTAT3 (Tyr705) expression of NOK group,and there was no statistically significant difference (P > 0.05).100 U/ml and 500 U/ml of interferons alpha could stimulate the increases of pSTAT3 (Tyr705) expression of DOK and KB cells,and the differences were statistically significant (P < 0.05).While they had no effect on pSTAT1 (Tyr701) expression.CP-690550 could effectively reduce the pSTAT3 DOK and KB cells (Tyr705) expression,and the differences were statistically significant (P < 0.05).Western blot showed that there were expression of SOCS1 and SOCS3 in control group.Interferons alpha and CP-690550 had no effect on SOCS1 and SOCS3 expression of NOK cell group,and there was no statistically significant difference (P > 0.05).100 U/ml and 500 U/ml of interferons alpha could stimulate the increase of SOCS 1 expression of DOK and KB cells,and differences were statistically significant (P < 0.05).For the expression of SOCS3,no influence.CP-690550 could effectively reduce the expression of SOCS1 of DOK and KB cells,and the differences were statistically significant (P < 0.05).Conclusions Interferons alpha activate DOK JAK1 and KB cells and the expression of JAK2,mainly JAK1 activation.Interferons alpha,by activating DOK JAK1 and KB cells and the expression of JAK2,promote STAT3 phosphorylation in Tyr705 locus.Interferons alpha,by promoting STAT3 phosphorylation,further promote the expression of SOCS1,which plays the role in inhibiting interferons alpha and reducing the apoptosis.
    • 胡若飞; 徐跃洋; 张二利; 吴俊军
    • 摘要: JAK3(Janus kinase 3)为酪氨酸蛋白激酶家族成员,研究证实其参与JAK-STAT通路信号传递,JAK3活性的改变在类风湿性关节炎等疾病的发病中是一个重要的诱因.JAK3活性的调控在多种疾病的治疗中起着至关重要的作用,针对该激酶的抑制剂已经有许多相关研究,数种抑制剂表现出了很好的JAK3选择性和抑制活性,托法替尼等抑制剂已经通过了临床试验,被批准用于类风湿性关节炎的治疗中.而与此同时,很多JAK3抑制剂在抑制JAK3活性、治疗疾病的同时,同时有一定的不良反应,有待于进一步的改良.本文将对JAK3及其抑制剂的研究现状进行概述,为已有JAK3抑制剂的进一步改良和新的抑制剂的开发提供参考.
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