Trembley Janeen H, Hu Dongli, Slaughter Clive A, Lahti Jill M, Kidd Vincent J
Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
J Biol Chem. 2003 Jan 24;278(4):2265-70. doi: 10.1074/jbc.M207518200. Epub 2002 Nov 11.
The PITSLRE protein kinases, hereafter referred to as cyclin-dependent kinase 11 (CDK11) due to their association with cyclin L, are part of large molecular weight protein complexes that contain RNA polymerase II (RNAP II) as well as numerous transcription and RNA processing factors. Data presented here demonstrate that the influence of CDK11(p110) on transcription and splicing does not involve phosphorylation of the RNAP II carboxyl-terminal domain by CDK11(p110). We have isolated a DRB- and heparin-sensitive protein kinase activity that co-purifies with CDK11(p110) after ion exchange and affinity purification chromatography. This protein kinase was identified as casein kinase 2 (CK2) by immunoblot and mass spectrometry analyses. In addition to the RNAP II carboxyl-terminal domain, CK2 phosphorylates the CDK11(p110) amino-terminal domain. These data suggest that CDK11(p110) isoforms participate in signaling pathways that include CK2 and that its function may help to coordinate the regulation of RNA transcription and processing events. Future experiments will determine how phosphorylation of CDK11(p110) by CK2 specifically affects RNA transcription and/or processing events.
PITSLRE蛋白激酶，因其与细胞周期蛋白L相关，以下简称为细胞周期蛋白依赖性激酶11（CDK11），是大分子量蛋白复合物的一部分，该复合物包含RNA聚合酶II（RNAP II）以及众多转录和RNA加工因子。本文提供的数据表明，CDK11（p110）对转录和剪接的影响并不涉及CDK11（p110）对RNAP II羧基末端结构域的磷酸化作用。我们分离出了一种对5,6 - 二氯 - 1 - β - D - 呋喃核糖基苯并咪唑（DRB）和肝素敏感的蛋白激酶活性，在离子交换和亲和纯化色谱后，它与CDK11（p110）共同纯化。通过免疫印迹和质谱分析，该蛋白激酶被鉴定为酪蛋白激酶2（CK2）。除了RNAP II羧基末端结构域，CK2还可磷酸化CDK11（p110）的氨基末端结构域。这些数据表明，CDK11（p110）亚型参与了包括CK2在内的信号通路，其功能可能有助于协调RNA转录和加工事件的调控。未来的实验将确定CK2对CDK11（p110）的磷酸化如何具体影响RNA转录和/或加工事件。
