Identification of CK2 as the kinase that phosphorylates Pax3 at Ser209 in early myogenic differentiation.
Identification of CK2 as the kinase that phosphorylates Pax3 at Ser209 in early myogenic differentiation.
复制标题
鉴定 CK2 作为早期肌原性分化中使 Pax3 Ser209 磷酸化的激酶。
DOI：
10.1016/j.bbrc.2012.09.141
复制
发表时间：
2012
影响因子：
3.1
通讯作者：
Hollenbach,AndrewD
中科院分区：
文献类型：
--
作者：
Iyengar,AditiS;Loupe,JacobM;Miller,PatrickJ;Hollenbach,AndrewD
生肌转录因子Pax 3是转录因子配对类同源结构域家族的成员，在早期骨骼肌发育中发挥着重要作用。我们先前证明Pax3在三个特定的残基（Ser201，Ser205和Ser209）磷酸化，并且在这些位点的磷酸化模式在整个早期肌生成中发生变化。此外，我们证明了蛋白激酶CK2在Ser205处磷酸化Pax3，并且该磷酸化事件是随后由GSK 3 β磷酸化Ser201所需的。然而，在Ser209处磷酸化Pax3的激酶尚未被鉴定。在目前的工作中，我们使用标准的纯化方法和体外生化分析，以提供坚实的证据，确定蛋白激酶CK2磷酸化Pax3在Ser209。此外，我们定性地证明，当Ser205之前磷酸化时，CK2在Ser209处的Pax3磷酸化增强。综上所述，我们的研究结果使我们能够提出一种机制来描述整个早期肌生成的有序磷酸化的Pax3。
The myogenic transcription factor Pax3, a member of the paired class homeodomain family of transcription factors, plays an essential role in early skeletal muscle development. We previously demonstrated that Pax3 is phosphorylated at three specific residues (Ser201, Ser205, and Ser209) and that the pattern of phosphorylation at these sites changes throughout early myogenesis. Further, we demonstrated that the protein kinase CK2 phosphorylates Pax3 at Ser205 and that this phosphorylation event is required for the subsequent phosphorylation of Ser201 by GSK3β. However, the kinase that phosphorylates Pax3 at Ser209 has yet to be identified. In the present work we use standard purification methods and in vitro biochemical analyses to provide solid evidence identifying the protein kinase CK2 as phosphorylating Pax3 at Ser209. Further, we qualitatively demonstrate that the phosphorylation of Pax3 at Ser209 by CK2 is enhanced when Ser205 is previously phosphorylated. Taken together, our results allow us to propose a mechanism to describe the ordered phosphorylation of Pax3 throughout early myogenesis.