...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Activation of cyclin-dependent kinase 4 (cdk4) by mouse MO15-associated kinase.
【24h】

Activation of cyclin-dependent kinase 4 (cdk4) by mouse MO15-associated kinase.

机译：小鼠MO15相关激酶激活细胞周期蛋白依赖性激酶4（cdk4）。

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

摘要

The assembly of functional holoenzymes composed of regulatory D-type cyclins and cyclin-dependent kinases (cdks) is rate limiting for progression through the G1 phase of the mammalian somatic cell cycle. Complexes between D-type cyclins and their major catalytic subunit, cdk4, are catalytically inactive until cyclin-bound cdk4 undergoes phosphorylation on a single threonyl residue (Thr-172). This step is catalyzed by a cdk-activating kinase (CAK) functionally analogous to the enzyme which phosphorylates cdc2 and cdk2 at Thr-161/160. Here, we demonstrate that the catalytic subunit of mouse cdc2/cdk2 CAK (a 39-kDa protein designated p39MO15) can assemble with a regulatory protein present in either insect or mammalian cells to generate a CAK activity capable of phosphorylating and enzymatically activating both cdk2 and cdk4 in complexes with their respective cyclin partners. A newly identified 37-kDa cyclin-like protein (cyclin H [R. P. Fisher and D. O. Morgan, Cell 78:713-724, 1994]) can assemble with p39MO15 to activate both cyclin A-cdk2 and cyclin D-cdk4 in vitro, implying that CAK is structurally reminiscent of cyclin-cdk complexes themselves. Antisera produced to the p39MO15 subunit can completely deplete mammalian cell lysates of CAK activity for both cyclin A-cdk2 and cyclin D-cdk4, with recovery of activity in the resulting immune complexes. By using an immune complex CAK assay, CAK activity for cyclin A-cdk2 and cyclin D-cdk4 was detected both in quiescent cells and invariantly throughout the cell cycle. Therefore, although it is essential for the enzymatic activation of cyclin-cdk complexes, CAK appears to be neither rate limiting for the emergence of cells from quiescence nor subject to upstream regulatory control by stimulatory mitogens.
机译：由调节性D型细胞周期蛋白和细胞周期蛋白依赖性激酶（cdks）组成的功能性全酶的组装限制了通过哺乳动物体细胞周期的G1期进程的速率。 D型细胞周期蛋白与其主要催化亚基cdk4之间的复合物具有催化活性，直到与细胞周期蛋白结合的cdk4在单个苏酰基残基（Thr-172）上磷酸化为止。该步骤由功能上类似于在Thr-161 / 160处磷酸化cdc2和cdk2的酶的cdk激活激酶（CAK）催化。在这里，我们证明了小鼠cdc2 / cdk2 CAK的催化亚基（称为p39MO15的39 kDa蛋白）可以与昆虫或哺乳动物细胞中存在的调节蛋白组装，以产生能够磷酸化和酶促激活cdk2和cdk的CAK活性。 cdk4与各自的细胞周期蛋白伴侣结合。新鉴定的37 kDa细胞周期蛋白样蛋白（细胞周期蛋白H [RP Fisher和DO Morgan，Cell 78：713-724，1994]）可以与p39MO15组装在一起，以在体外激活cyclin A-cdk2和cyclin D-cdk4。 CAK在结构上让人联想到细胞周期蛋白-cdk复合物本身。产生的针对p39MO15亚基的抗血清可以完全耗尽针对细胞周期蛋白A-cdk2和细胞周期蛋白D-cdk4的CAK活性的哺乳动物细胞裂解物，并在所得免疫复合物中恢复活性。通过使用免疫复合物CAK分析，不仅在静止细胞中而且在整个细胞周期中均检测到针对细胞周期蛋白A-cdk2和细胞周期蛋白D-cdk4的CAK活性。因此，尽管对于细胞周期蛋白-cdk复合物的酶促活化是必不可少的，但CAK似乎既不限制细胞从静止状态出现的速率，也不受刺激性有丝分裂原的上游调节控制。

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