The effector loop and prenylation site of R-Ras are involved in the regulation of integrin function
The effector loop and prenylation site of R-Ras are involved in the regulation of integrin function
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DOI：
10.1038/sj.onc.1203876
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发表时间：
2000-10-12
期刊：
影响因子：
8
通讯作者：
Hughes, PE
中科院分区：
文献类型：
--
作者：
Oertli, B;Han, J;Hughes, PE
密切相关的小 GTP 结合蛋白 H-Ras 和 R-Ras 对整合素细胞粘附受体的调节具有相反的作用。为了深入了解 R-Ras 在整合素功能调节以及与下游效应子相互作用方面的特性，我们对包含效应子结合域和 C 末端异戊二烯化位点突变的 R-Ras 变体进行了分析。我们发现下游效应器 PI 3 激酶的激活对效应器结合域的突变敏感，与效应器 Ral-GDS、Raf-1 和新型效应器 Norel 的结合也是如此。此外，效应器结合环和 C 端异戊二烯化基序的特定突变损害了 R-Ras 调节 CHO 细胞中整合素功能的能力。然而，R-Ras 效应器环突变体结合和激活已知效应器的能力与其调节整合素功能的能力并不相关。因此，已知的 R-Ras 效应子对于调节整合素激活并不重要，至少在 CHO 细胞中是这样。因此，这些研究提供了对 R-Ras 与其候选效应子之间相互作用的结构基础的深入了解，并表明这种 GTPase 可以调节细胞粘附的新机制的存在。
The closely related small GTP-binding proteins H-Ras and R-Ras have opposing effects on the regulation of integrin cell adhesion receptors, To gain insight into the properties of R-Ras with respect to the regulation of integrin function and interactions with downstream effecters we performed an analysis of R-Ras variants containing mutations in the effector binding domain and C-terminal prenylation site. We found that the activation of the downstream effector PI 3-kinase was sensitive to mutations in the effector binding domain, as was the binding to the effecters, Ral-GDS, Raf-1 and the novel effector Norel, Furthermore, specific mutations in the effector binding loop and C-terminal prenylation motif impaired the ability of R-Ras to regulate integrin function in CHO cells. However, the ability of the R-Ras effector loop mutants to bind, and activate known effecters did not correlate with their ability to regulate integrin function. Thus, the known R-Ras effecters are not critical for regulating integrin activation, at least in CHO cells, Consequently, these studies provide insight into the structural basis of the interactions between R-Ras and its candidate effecters and suggest the existence of novel mechanisms through which this GTPase could regulate cell adhesion.