Pheromone induction promotes Ste11 degradation through a MAPK feedback and ubiquitin-dependent mechanism
Pheromone induction promotes Ste11 degradation through a MAPK feedback and ubiquitin-dependent mechanism
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DOI：
10.1073/pnas.142034399
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发表时间：
2002-07-09
影响因子：
11.1
通讯作者：
Errede, B
中科院分区：
文献类型：
--
作者：
Esch, RK;Errede, B
Ste11是酿酒酵母中丝裂原活化蛋白激酶(MAPK)级联中的丝裂原活化蛋白激酶，它介导交配、高渗透压甘油和丝状生长反应。我们发现信息素对交配途径的刺激通过MAPK反馈和泛素依赖的机制促进Ste11的加速周转。这种降解是特定于途径的，因为Ste11在高渗透压甘油途径激活期间是稳定的。由于Ste11的稳态量在信息素诱导过程中没有显著变化，我们推测MAPK激活的维持涉及到重复的循环，在这个循环中，幼稚的Ste11被激活，然后被靶向降解。该模型预测，一旦上游信号减弱，活性Ste11的消除将迅速减少MAPK的激活。这一预测得到了以下发现的证实：在信息素诱导过程中阻止泛素依赖的Ste11降解取消了MAPK激活的特征衰减曲线。
Ste11 is the mitogen-activated protein kinase (MAPK) kinase kinase in the MAPK cascades that mediate mating, high osmolarity glycerol, and filamentous growth responses in Saccharomyces cerevisiae. We show stimulation of the mating pathway by pheromone promotes an accelerated turnover of Ste11 through a MAPK feedback and ubiquitin-dependent mechanism. This degradation is pathway specific, because Ste11 is stable during activation of the high osmolarity glycerol pathway. Because the steady-state amount of Ste11 does not change significantly during pheromone induction, we infer that maintenance of MAPK activation involves repeated cycles in which naive Ste11 is activated and then targeted for degradation. This model predicts that elimination of active Ste11 would rapidly curtail MAPK activation upon attenuation of the upstream signal. This prediction is confirmed by the finding that blocking ubiquitin-dependent Ste11 degradation during pheromone induction abolishes the characteristic attenuation profile for MAPK activation.