B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERK
B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERK
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DOI：
10.1038/sj.emboj.7600980
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发表时间：
2006-02-22
期刊：
影响因子：
11.4
通讯作者：
Porteu, F
中科院分区：
文献类型：
--
作者：
Letourneux, C;Rocher, G;Porteu, F
蛋白磷酸酶2A （PP2A）作用于细胞外信号调节激酶（ERK）信号通路中的几种激酶，但是否有特定的全酶使ERK去磷酸化以及这种活性是否在有丝分裂刺激过程中受到控制尚不清楚。通过RNA干扰和PP2A B调控亚基的过表达，我们发现PP2A家族成员B56（而不是B）增加了ERK的去磷酸化，但不影响其被MEK激活。生长因子诱导早期基因产物和ERK底物IEX- 1 （ier3）产生相反的作用，逆转B56- pp2a介导的ERK去磷酸化。IEX- 1独立结合B56亚基和pERK，增强ERK在该复合物中保守的Ser/ Pro位点对B56的磷酸化，并触发催化亚基的解离。这是首次证明含有B56的PP2A参与ERK去磷酸化，以及B56特异性细胞蛋白抑制剂以ERK依赖的方式调节其活性。此外，我们的研究结果提出了ERK信号传导的新范式，其中与底物相关的ERK可以使附近的蛋白质转磷酸化。
The protein phosphatase 2A ( PP2A) acts on several kinases in the extracellular signal- regulated kinase ( ERK) signaling pathway but whether a specific holoenzyme dephosphorylates ERK and whether this activity is controlled during mitogenic stimulation is unknown. By using both RNA interference and overexpression of PP2A B regulatory subunits, we show that B56, but not B, family members of PP2A increase ERK dephosphorylation, without affecting its activation by MEK. Induction of the early gene product and ERK substrate IEX- 1 ( ier3) by growth factors leads to opposite effects and reverses B56- PP2A-mediated ERK dephosphorylation. IEX- 1 binds to B56 subunits and pERK independently, enhances B56 phosphorylation by ERK at a conserved Ser/ Pro site in this complex and triggers dissociation from the catalytic subunit. This is the first demonstration of the involvement of B56- containing PP2A in ERK dephosphorylation and of a B56- specific cellular protein inhibitor regulating its activity in an ERK- dependent fashion. In addition, our results raise a new paradigm in ERK signaling in which ERK associated to a substrate can transphosphorylate nearby proteins.