Cell cycle-dependent phosphorylation of Disabled-2 by cdc2
Cell cycle-dependent phosphorylation of Disabled-2 by cdc2
复制标题
DOI：
10.1038/sj.onc.1206767
复制
发表时间：
2003-07-17
期刊：
影响因子：
8
通讯作者：
Hall, RA
中科院分区：
文献类型：
--
作者：
He, JQ;Xu, HG;Hall, RA
Disabled-2（Dab 2;也称为p96和DOC-2）是一种信号转导蛋白，参与细胞生长的控制。已知Dab 2是一种磷蛋白，但对磷酸化Dab 2的激酶知之甚少。我们已经发现，Dab 2磷酸化在细胞周期的有丝分裂期显著增加。这种磷酸化被roscovitine阻断，roscovitine是一种细胞周期蛋白依赖性激酶的选择性抑制剂。Dab 2与细胞周期蛋白依赖性激酶cdc 2强烈共免疫沉淀，纯化的cdc 2可以在体外多个位点磷酸化纯化的Dab 2融合蛋白。Cdc 2对Dab 2的细胞磷酸化促进Dab 2与Pir 1的结合，Pir 1是调节Dab 2去磷酸化速率的肽基脯氨酰异构酶。这些研究结果表明，Dab 2是差异磷酸化的细胞周期过程中的cdc 2和提供一个潜在的反馈机制，Dab 2抑制细胞生长和增殖可能受到调节。
Disabled-2 (Dab2; also known as p96 and DOC-2) is a signal transduction protein that has been implicated in the control of cell growth. Dab2 is known to be a phosphoprotein, but little is known about the kinases that phosphorylate Dab2. We have found that Dab2 phosphorylation is markedly increased during the mitosis phase of the cell cycle. This phosphorylation is blocked by roscovitine, a selective inhibitor of cyclin-dependent kinases. Dab2 robustly coimmunoprecipitates from cells with the cyclin-dependent kinase cdc2, and purified cdc2 can phosphorylate purified Dab2 fusion proteins in vitro on multiple sites. Cellular phosphorylation of Dab2 by cdc2 promotes the association of Dab2 with Pir1 a peptidylprolyl isomerase that regulates the rate of Dab2 dephosphorylation. These findings reveal that Dab2 is differentially phosphorylated during the cell cycle by cdc2 and provide a potential feedback mechanism by which Dab2 inhibition of cell growth and proliferation may be regulated.