Raf-independent, PP2A-dependent MEK activation in response to ERK silencing.
Raf-independent, PP2A-dependent MEK activation in response to ERK silencing.
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DOI：
10.1016/j.bbrc.2009.05.082
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发表时间：
2009-08-07
影响因子：
3.1
通讯作者：
Ceryak, Susan
中科院分区：
文献类型：
--
作者：
Bae, Dongsoon;Ceryak, Susan
ERK和MEK在信号转导中的生物学作用一直存在争议。本研究的目的是通过RNAi方法来确定ERK 1/2在通过ERK-MAPK级联的信号传导中的作用。erk 1或erk 2 siRNA的瞬时转染使人肺成纤维细胞中相应的蛋白水平降低至3 - 8%。有趣的是，个体ERK亚型沉默导致替代ERK亚型磷酸化的2倍相互增加，而相应的总蛋白表达没有变化。此外，由于ERK 1和ERK 2沉默的组合，MEK被过度磷酸化，但在单独的ERK 1或ERK 2沉默细胞中不受影响。这种MEK的过度激活不是由于Raf家族成员的激活，而是与PP 2A下调有关。这些数据突出了正常细胞中反馈环的存在，其中ERK沉默与PP 2A活性降低和随后的MEK活化相关。
Biological roles of ERK and MEK in signal transduction have been controversial. The aim of the current study was to determine the role of ERK1/2 in signaling through the ERK-MAPK cascade by using RNAi methodology. Transient transfection of erk1 or erk2 siRNA decreased the respective protein level to 3 - 8% in human lung fibroblasts. Interestingly, individual ERK isoform silencing resulted in a 2-fold reciprocal increase in phosphorylation of the alternate ERK isoform, with no change in respective total protein expression. Moreover, MEK was hyperphosphorylated as a result of combined ERK1 and ERK2 silencing, but was unaffected in individual ERK1 or ERK2 silenced cells. This hyperactivation of MEK was not due to activation of Raf family members, but rather was associated with PP2A downregulation. These data highlight the existence of a feedback loop in normal cells whereby ERK silencing is associated with decreased PP2A activity and consequent MEK activation.
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影响因子：
5.3
作者：
Lefloch, Renaud;Pouyssegur, Jacques;Lenormand, Philippe
通讯作者：
Lenormand, Philippe
影响因子：
11.2
作者：
Daouti, Sherif;Wang, Huisheng;Niu, Huifeng
通讯作者：
Niu, Huifeng
影响因子：
4.3
作者：
Lal, Madhu A.;Bae, Dongsoon;Ceryak, Susan
通讯作者：
Ceryak, Susan
影响因子：
4.3
作者：
Ceryak, S;Zingariello, C;Patierno, SR
通讯作者：
Patierno, SR
影响因子：
4.8
作者：
Adams, DG;Coffee, RL;Wadzinski, BE
通讯作者：
Wadzinski, BE