Ca2+/Calmodulin-dependent Protein Kinase II Promotes Cell Cycle Progression by Directly Activating MEK1 and Subsequently Modulating p27 Phosphorylation (Publication with Expression of Concern. See vol. 295, pg. 8879, 2020) (Withdrawn Publication. See vol. 296, 2021) (Withdrawn Publication. See vol. 296, 2021)
Ca2+/Calmodulin-dependent Protein Kinase II Promotes Cell Cycle Progression by Directly Activating MEK1 and Subsequently Modulating p27 Phosphorylation (Publication with Expression of Concern. See vol. 295, pg. 8879, 2020) (Withdrawn Publication. See vol. 296, 2021) (Withdrawn Publication. See vol. 296, 2021)
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DOI：
10.1074/jbc.m805483200
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发表时间：
2009-01-30
影响因子：
4.8
通讯作者：
Cao, Xuetao
中科院分区：
文献类型：
--
作者：
Li, Nan;Wang, Chunmei;Cao, Xuetao
Cell proliferation is regulated by integration of multiple pathways, such as MAPK, phosphatidylinositol 3'-kinase, protein kinase C, and Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling, determining whether the cell proceeds into cell cycle progression. Recently, we have demonstrated that a novel endogenous CaMKII-inhibitory protein, hCaMKIIN alpha, suppresses tumor growth by inducing cell cycle arrest via p27 stabilization, accompanied by MEK/ERK deactivation. The data indicate a potential link between Ca2+/CaMKII and other signaling pathways, such as MAPK signaling. However, the detailed mechanisms of cross-talks between these important pathways on cell cycle regulation have not been specified. Here we report that CaMKII, in colon adenocarcinoma cells, activates MEK/ERK, which is responsible for the phosphorylation and subsequent proteasomal degradation of p27, thus causing the promotion of the S-G(2)/M transition of cell cycle progression. Importantly, we found that CaMKII can bind to MEK1 and that active CaMKII directly phosphorylates MEK1 in vitro, which could be abrogated by CaMKII inhibitor. Besides, ERK2 can directly interact with and phosphorylate p27. This is the first demonstration that CaMKII interplays with MEK1 and regulates p27 phosphorylation in the cell cycle progression. These findings provide mechanistic evidence for the cross-talk between CaMKII and MAPK signaling, which converges in MEK/ERK activation in the regulation of cell cycle progression.
