GROWTH FACTOR-STIMULATED MAP KINASE INDUCES RAPID RETROPHOSPHORYLATION AND INHIBITION OF MAP KINASE KINASE (MEK1)
GROWTH FACTOR-STIMULATED MAP KINASE INDUCES RAPID RETROPHOSPHORYLATION AND INHIBITION OF MAP KINASE KINASE (MEK1)
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DOI：
10.1016/0014-5793(94)00475-7
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发表时间：
1994-06-13
期刊：
影响因子：
3.5
通讯作者：
POUYSSEGUR, J
中科院分区：
文献类型：
--
作者：
BRUNET, A;PAGES, G;POUYSSEGUR, J
MAP激酶模块（Raf/MAPKKK-MAPKK-MAPK）已被证明在有丝分裂刺激后被顺序激活。在这里，我们通过位点定向诱变证明，MAPK能够在体外对两个苏氨酸残基Thr-292和Thr-386上对其自身的激活子MAPKK进行反磷酸化，并且这些位点在体内也会被磷酸化。对野生型MAPKK和不能被MAPK磷酸化的突变体的血清介导激活动力学的比较表明，这种逆转录磷酸化可能参与了体内级联反应的负反馈控制。
The MAP kinase module (Raf/MAPKKK-MAPKK-MAPK) has been shown to be sequentially activated after mitogenic stimulation. Here we demonstrate, by site directed mutagenesis, that MAPK is able to retrophosphorylate its own activator, MAPKK, on two threonine residues Thr-292 and Thr-386 in vitro, and that these sites are also phosphorylated in vivo. A comparison of the kinetics of serum-mediated activation of a wild-type MAPKK and of a mutant unable to undergo phosphorylation by MAPK suggests that this retrophosphorylation may be involved in a negative feedback control of the cascade in vivo.