• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >Ordered multi-site phosphorylation of the splicing factor ASF/SF2 by SRPK1
【24h】

Ordered multi-site phosphorylation of the splicing factor ASF/SF2 by SRPK1

机译：剪接因子ASF / SF2的SRPK1有序多位磷酸化

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

The human alternative splicing factor ASF/SF2, an SR (serine-arginine-rich) protein involved in mRNA splicing control, is activated by the multisite phosphorylation of its C-terminal RS domain, a segment containing numerous arginine-serine dipeptide repeats. The protein kinase responsible for this modification, SR-specific protein kinase 1 (SRPK1), catalyzes the selective phosphorylation of approximately a dozen serines in only the N-terminal portion of the RS domain (RS1). To gain insights into the nature of selective phosphate incorporation in ASF/SF2, region-specific phosphorylation in the RS domain was monitored as a function of reaction progress. Arg-to-Lys mutations were made at several positions to produce unique protease cleavage sites that separate the RS domain into identifiable N- and C-terminal phosphopeptides upon treatment with lysyl endoproteinase. These studies reveal that SRPK1 docks near the C-terminus of the RS1 segment and then moves in an N-terminal direction along the RS domain. Multiple quadruple Ser-to-Ala and deletion mutations did not disrupt the phosphorylation of other sites regardless of position, suggesting that the active site of SRPK1 docks in a flexible manner at the center of the RS domain. Taken together, these data suggest that SRPK1 uses a unique 'grab-and-pull' mechanism to control the regiospecific phosphorylation of its protein substrate. Published by Elsevier Ltd.
机译：人类选择性剪接因子ASF / SF2是一种参与mRNA剪接控制的SR（富含丝氨酸精氨酸）蛋白，通过其C端RS结构域（包含许多精氨酸-丝氨酸二肽重复序列的片段）的多位磷酸化而被激活。负责这种修饰的蛋白激酶SR特异性蛋白激酶1（SRPK1）仅在RS结构域（RS1）的N端部分催化大约十二个丝氨酸的选择性磷酸化。为了深入了解选择性磷酸盐掺入ASF / SF2的性质，根据反应进程对RS结构域中的区域特异性磷酸化进行了监测。在几个位置进行了Arg-Lys突变，以产生独特的蛋白酶切割位点，该位点在用赖氨酰内蛋白酶处理后将RS结构域分离为可识别的N和C末端磷酸肽。这些研究表明，SRPK1在RS1段的C末端附近停靠，然后沿RS域在N端方向移动。无论位置如何，多个四位Ser-to-Ala和缺失突变均不会破坏其他位点的磷酸化，这表明SRPK1的活性位点以灵活的方式停靠在RS结构域的中心。综上所述，这些数据表明SRPK1使用独特的“抓拉”机制来控制其蛋白底物的区域特异性磷酸化。由Elsevier Ltd.发布

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