• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of cellular biochemistry. >An osteoclastic protein-tyrosine phosphatase is a potential positive regulator of the c-Src protein-tyrosine kinase activity: a mediator of osteoclast activity.
【24h】

An osteoclastic protein-tyrosine phosphatase is a potential positive regulator of the c-Src protein-tyrosine kinase activity: a mediator of osteoclast activity.

机译：破骨细胞蛋白酪氨酸磷酸酶是c-Src蛋白酪氨酸激酶活性的潜在正调节剂：破骨细胞活性的介体。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

This study tested the hypothesis that an osteoclastic protein-tyrosine phosphatase, PTP-oc, enhances osteoclast activity through c-Src activation. The effects of several resorption activators and inhibitors on PTP-oc expression, resorption activity, and c-Src activation were determined in rabbit osteoclasts. PTP-oc expression was assayed with immunoblots and semi-quantitative RT-PCR. Osteoclastic activity was determined by the resorption pit assay; and c-Src activation was monitored by P-tyr527 (PY527) dephosphorylation, and in vitro kinase assay. Treatment of osteoclasts with PTH, PGE2, 1,25(OH)2D3, IL-1, but not RANKL or IL-6, significantly stimulated resorption activity, increased PTP-oc mRNA and protein levels, and reduced c-Src PY527 level with corresponding activation of c-Src protein-tyrosine kinase activity. The PTP-oc antisense phosphorothioated oligo treatment blocked the basal and IL-1alpha-mediated, but not RANKL-mediated, resorption activity of isolated osteoclasts. The antisense oligo treatment also significantly reduced the average depth of resorption pits created by rabbit osteoclasts under basal conditions. Calcitonin and alendondrate, significantly reduced resorption activity and PTP-oc expression, and increased c-Src PY527 with corresponding reduction in its PTK activity. The cellular PTP-oc protein level correlated with the resorption activity. Among the various signaling proteins co-immunoprecipitated with PTP-oc, the resorption effectors caused corresponding changes in the tyrosyl phosphorylation level of only c-Src. The GST-PTP-oc fusion protein dephosphorylated PY-527-containing c-Src peptide in time- and dose-dependent manner in vitro. In summary, (1) PTP-oc is regulated in part at transcriptional level, (2) upregulation of PTP-oc in osteoclasts led to c-Src activation, and (3) PY527 of c-Src may be a cellular substrate of PTP-oc. These findings are consistent with the hypothesis that PTP-oc is a positive regulator of c-Src in osteoclasts.
机译：这项研究检验了以下假设：破骨细胞蛋白酪氨酸磷酸酶PTP-oc通过c-Src激活增强破骨细胞活性。在兔破骨细胞中测定了几种吸收激活剂和抑制剂对PTP-oc表达，吸收活性和c-Src激活的影响。用免疫印迹和半定量RT-PCR测定PTP-oc表达。破骨活性通过吸收凹坑测定法测定。并通过P-tyr527（PY527）的去磷酸化和体外激酶测定来监测c-Src的活化。用PTH，PGE2、1,25（OH）2D3，IL-1（而不是RANKL或IL-6）治疗破骨细胞，可显着刺激吸收活性，增加PTP-oc mRNA和蛋白水平，并降低c-Src PY527水平， c-Src蛋白酪氨酸激酶活性的相应激活。 PTP-oc反义硫代磷酸酯化寡核苷酸处理阻断了分离的破骨细胞的基础和IL-1alpha介导的但不是RANKL介导的吸收活性。反义寡核苷酸处理还显着降低了在基础条件下兔破骨细胞产生的平均吸收凹坑深度。降钙素和阿仑膦酸盐显着降低了吸收活性和PTP-oc表达，并增加了c-Src PY527，同时相应降低了其PTK活性。细胞中的PTP-oc蛋白水平与吸收活性相关。在与PTP-oc共免疫沉淀的各种信号蛋白中，吸收效应子仅引起c-Src酪氨酸磷酸化水平的相应变化。在体外，GST-PTP-oc融合蛋白以时间和剂量依赖性方式使含PY-527的c-Src肽脱磷酸化。总之，（1）PTP-oc在转录水平上受到部分调节，（2）破骨细胞中PTP-oc的上调导致c-Src活化，并且（3）c-Src的PY527可能是PTP的细胞底物-oc。这些发现与PTP-oc是破骨细胞中c-Src的正调节剂的假设相一致。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号