Involvement of protein kinase PKN1 in G2/M delay caused by arsenite
Involvement of protein kinase PKN1 in G2/M delay caused by arsenite
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DOI：
10.1002/mc.20087
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发表时间：
2005-05-01
影响因子：
4.6
通讯作者：
Ono, Y
中科院分区：
文献类型：
--
作者：
Isagawa, T;Takahashi, M;Ono, Y
PKN 1是一种丝氨酸/苏氨酸蛋白激酶，已报道其介导细胞对应激的反应。我们在这里表明，在响应砷暴露，PKN 1激酶活性被刺激，这是与PKN 1的Cdc 25 C和延迟有丝分裂进入的结合增加。PKN 1在介导砷诱导的G（2）/M延迟中的作用得到了以下发现的支持：在HeLa细胞中表达PKN 1的组成型活性形式（PKN 1AF 3）延迟细胞周期的有丝分裂进入。进一步的实验表明，PKN 1直接磷酸化Cdc 25 C中的丝氨酸216（Ser 216），然后促进Cdc 25 C和14-3-3之间的关联。值得注意的是，Cdc 25 C（S21 6A）的磷酸化突变体的表达部分废除了细胞周期停滞响应亚砷酸盐。总之，我们的研究结果表明，PKN 1介导砷诱导的G2/M转换的延迟结合和磷酸化Cdc 25 C。(c)2005 Wiley-Liss，Inc.
PKN1 is a serine/threonine protein kinase that has been reported to mediate cellular response to stress. We show here that in response to arsenite exposure, PKN1 kinase activity was stimulated, which was associated with increased binding of PKN1 to Cdc25C and delayed mitotic entry. A role for PKN1 in mediating arsenite-induced G(2)/M delay was supported by the finding that expression of a constitutively active form of PKN1 (PKN1AF3) in HeLa cells delayed the mitotic entry of cell cycle. Further experiments indicate that PKN1 directly phosphorylated serine 216 (Ser216) in Cdc25C, which then facilitated association between Cdc25C and 14-3-3. Significantly, expression of a phosphorylation mutant of Cdc25C (S21 6A) partially abrogated the cell-cycle arrest in response to arsenite. Together, our results suggest that PKN1 mediates arsenite-induced delay of the G2/M transition by binding to and phoshorylating Cdc25C. (c) 2005 Wiley-Liss, Inc.