Kinase suppressor of Ras couples Ras to the ERK cascade during T cell development
Kinase suppressor of Ras couples Ras to the ERK cascade during T cell development
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DOI：
10.4049/jimmunol.173.2.986
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发表时间：
2004-07-15
影响因子：
4.4
通讯作者：
Alberola-Ila, J
中科院分区：
文献类型：
--
作者：
Laurent, MN;Ramirez, DM;Alberola-Ila, J
Ras信号传导对许多发育过程至关重要，需要精确协调多个下游组件之间的相互作用。实现这种调节的一种机制是通过使用协调多分子复合物组装的支架分子。最近，Ras的支架分子激酶抑制因子（KSR）在遗传筛选中被分离为Ras信号转导的修饰剂，尽管其对调节Ras介导的其不同下游效应物的激活的贡献还不清楚。我们分析了KSR在正选择过程中连接Ras与ERK级联反应中的作用。我们的研究结果表明，KSR过表达干扰T细胞发育，这种作用需要KSR和MEK之间的直接相互作用。这种功能效应与KSR在过度表达时将Ras从ERK级联中解偶联的能力相关。
Ras signaling is critical for many developmental processes and requires the precise coordination of interactions among multiple downstream components. One mechanism by which this regulation is achieved is through the use of scaffolding molecules that coordinate the assembly of multimolecular complexes. Recently, the scaffolding molecule kinase suppressor of Ras (KSR) was isolated in genetic screens as a modifier of Ras signaling, although its contribution to regulating Ras-mediated activation of its different downstream effectors is not well understood. We have analyzed the role of KSR in linking Ras to the ERK cascade during positive selection. Our results demonstrate that KSR overexpression interferes with T cell development, an effect that requires the direct interaction between KSR and MEK. This functional effect correlates with the ability of KSR to uncouple Ras from the ERK cascade when overexpressed.