KSR is a scaffold required for activation of the ERK/MAPK module
KSR is a scaffold required for activation of the ERK/MAPK module
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DOI：
10.1101/gad.962902
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发表时间：
2002-02-15
影响因子：
10.5
通讯作者：
Therrien, M
中科院分区：
文献类型：
--
作者：
Roy, F;Laberge, G;Therrien, M
通过ERK/MAPK途径调节信号传播的机制仍然知之甚少。有几种蛋白质被怀疑在这一过程中起关键作用。其中之一是Ras激酶抑制因子（KSR），这是先前在果蝇和秀丽隐杆线虫的Ras依赖基因筛选中发现的一种成分。在这里，我们发现KSR在ERK/MAPK模块中作用于MEK的上游。与此一致，我们发现KSR促进了RAF对MEK的磷酸化。我们进一步表明，KSR与RAF和MEK独立结合，这些相互作用导致RAF/MEK复合物的形成，从而使RAF靠近其底物MEK。这些发现表明，KSR作为一个支架，组装RAF/MEK功能对。
Mechanisms that regulate signal propagation through the ERK/MAPK pathway are still poorly understood. Several proteins are suspected to play critical roles in this process. One of these is Kinase Suppressor of Ras (KSR), a component previously identified in RAS-dependent genetic screens in Drosophila and Caenorhabditis elegans. Here, we show that KSR functions upstream of MEK within the ERK/MAPK module. In agreement with this, we found that KSR facilitates the phosphorylation of MEK by RAF. We further show that KSR associates independently with RAF and MEK, and that these interactions lead to the formation of a RAF/MEK complex, thereby positioning RAF in close proximity to its substrate MEK. These findings suggest that KSR functions as a scaffold that assembles the RAF/MEK functional pair.