...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Convergence of mitogenic signalling cascades from diverse classes of receptors at the cyclin D-cyclin-dependent kinase-pRb-controlled G1 checkpoint.
【24h】

Convergence of mitogenic signalling cascades from diverse classes of receptors at the cyclin D-cyclin-dependent kinase-pRb-controlled G1 checkpoint.

机译：来自细胞周期蛋白D-细胞周期蛋白依赖性激酶-pRb控制的G1检查点的各种受体的有丝分裂信号级联的收敛。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The commitment of mammalian cells in late G1 to replicate the genome and divide in response to mitogenic growth factors operating via tyrosine kinase receptors depends on phosphorylation of the retinoblastoma protein (pRb), a process controlled by cyclin D-associated cyclin-dependent kinases (cdks) and their inhibitors. This study addressed the issue of whether also other mitogenic signalling cascades require activation of cyclin D-associated kinases or whether any mitogenic pathway can bypass the cyclin D-pRb checkpoint. We show that mitogenic signal transduction pathways from three classes of receptors, the membrane tyrosine kinase receptors activated by serum mitogens or epidermal growth factor, estrogen receptors triggered by estradiol, and the cyclic AMP-dependent signalling from G-protein-coupled thyrotropin receptors, all converge and strictly require the cyclin D-cdk activity to induce S phase in human MCF-7 cells and/or primary dog thyrocytes. Combined microinjection and biochemical approaches showed that whereas these three mitogenic cascades are sensitive to the p16 inhibitor of cdk4/6 and/or cyclin D1-neutralizing antibody and able to induce pRb kinase activity, their upstream biochemical routes are distinct as demonstrated by their differential sensitivity to lovastatin and requirements for mitogen-activated protein kinases whose sustained activation is seen only in the growth factor-dependent pathway. Taken together, these results support the candidacy of the cyclin D-cdk-pRb interplay for the convergence step of multiple signalling cascades and a mechanism contributing to the restriction point switch.
机译：在G1晚期，哺乳动物细胞对复制基因组和响应通过酪氨酸激酶受体起作用的促有丝分裂生长因子而分裂的承诺取决于视网膜母细胞瘤蛋白（pRb）的磷酸化，该过程由细胞周期蛋白D相关的细胞周期蛋白依赖性激酶（cdks）控制）及其抑制剂。这项研究解决了其他有丝分裂信号级联反应是否也需要激活细胞周期蛋白D相关激酶的问题，或者是否任何有丝分裂途径都可以绕过细胞周期蛋白D-pRb检查点的问题。我们显示出来自三类受体的促有丝分裂信号转导途径：由血清促有丝分裂剂或表皮生长因子激活的膜酪氨酸激酶受体，由雌二醇触发的雌激素受体以及由G蛋白偶联促甲状腺激素受体产生的环AMP依赖性信号传导，所有聚合并严格要求细胞周期蛋白D-cdk活性诱导人MCF-7细胞和/或原代狗甲状腺细胞的S期。显微注射和生化方法相结合表明，尽管这三个促有丝分裂级联对cdk4 / 6和/或cyclin D1中和抗体的p16抑制剂敏感，并能够诱导pRb激酶活性，但它们的上游生化途径却有所区别洛伐他汀对丝裂原活化蛋白激酶的要求，其持续活化仅在生长因子依赖性途径中可见。综上所述，这些结果支持了细胞周期蛋白D-cdk-pRb相互作用对多个信号级联的收敛步骤的候选资格以及有助于限制点转换的机制。

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