C-elegans ksr-1 and ksr-2 have both unique and redundant functions and are required for MPK-1 ERK phosphorylation
C-elegans ksr-1 and ksr-2 have both unique and redundant functions and are required for MPK-1 ERK phosphorylation
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DOI：
10.1016/s0960-9822(02)00690-5
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发表时间：
2002-03-05
期刊：
影响因子：
9.2
通讯作者：
Sundaram, MV
中科院分区：
文献类型：
--
作者：
Ohmachi, M;Rocheleau, CE;Sundaram, MV
Ras激酶抑制因子(KSR)是一种正向调节RAS信号的保守蛋白，可作为Raf、MEK和ERK的支架[1]。然而，KSR的确切作用还不是很清楚，一些观察表明KSR可能是以平行途径起作用的。在线虫中，KSR-1只是特定的RAS介导的过程(有性成肌细胞迁移)所必需的，并且是其他RAS介导的发育事件的非必要的正向调节[2，3]。我们报道了第二个线虫KSR-2基因的存在，该基因在生殖系减数分裂过程中是RAS介导的信号转导所必需的，在排泄系统、两性外阴和雄性针状体的发育过程中与KSR-1具有冗余的功能。因此，虽然KSR-1和KSR-2基因仅在特定的RAS依赖过程中是单独需要的，但这两个基因在线虫RAS介导的信号转导的大多数方面似乎都是必需的。KSR-2；KSR-1双突变体具有强烈的ras样表型和严重降低或缺失的二磷酸化MPK-1 ERK水平，这一发现有力地支持了KSR促进Raf/MEK/ERK激酶级联的激活或维持的模型。
Kinase Suppressor of Ras (KSR) is a conserved protein that positively regulates Ras signaling and may function as a scaffold for Raf, MEK, and ERK [1]. However, the precise role of KSR is not well understood, and some observations have suggested that KSR might act in a parallel pathway. In C. elegans, ksr-1 is only required for a specific Ras-mediated process (sex myoblast migration) and is a nonessential positive regulator of other Ras-mediated developmental events [2, 3]. We report the existence of a second C. elegans ksr gene, ksr-2, which is required for Ras-mediated signaling during germline meiotic progression and functions redundantly with ksr-1 during development of the excretory system, hermaphrodite vulva, and male spicules. Thus, while the ksr-1 and ksr-2 genes are individually required only for specific Ras-dependent processes, together these two genes appear necessary for most aspects of Ras-mediated signaling in C. elegans. The finding that ksr-2; ksr-1 double mutants have strong ras-like phenotypes and severely reduced or absent levels of diphosphorylated MPK-1 ERK strongly supports models where KSR acts to promote the activation or maintenance of the Raf/MEK/ERK kinase cascade.