Signaling specificity by Ras family GTPases is determined by the full spectrum of effectors they regulate
Signaling specificity by Ras family GTPases is determined by the full spectrum of effectors they regulate
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DOI：
10.1128/mcb.24.11.4943-4954.2004
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发表时间：
2004-06-01
影响因子：
5.3
通讯作者：
McCormick, F
中科院分区：
文献类型：
--
作者：
Rodriguez-Viciana, P;Sabatier, C;McCormick, F
Ras家族GTP酶（RFG）调节控制多种生物过程的信号传导途径。如何实现密切相关的家庭成员之间的信号特异性知之甚少。我们已经采取了蛋白质组学的方法来通过RFG信号，我们已经分析了一组RFG与一组全面的已知和潜在的效应物的相互作用。我们已经发现RFG调节已知效应子家族的各种亚型的能力存在显著差异。我们还确定了几种蛋白质作为RFG的新型效应物，其对各种RFG具有不同的结合特异性。我们提出RFG之间的特异性是通过效应子家族的组合的差异调节以及通过效应子家族内不同亚型的选择性调节来实现的。理解RFG调控的信号通路的这种新的复杂性水平对于理解它们如何执行许多细胞功能是必要的。它还可能对治疗癌症等人类疾病产生重要影响。
Ras family GTPases (RFGs) regulate signaling pathways that control multiple biological processes. How signaling specificity among the closely related family members is achieved is poorly understood. We have taken a proteomics approach to signaling by RFGs, and we have analyzed interactions of a panel of RFGs with a comprehensive group of known and potential effectors. We have found remarkable differences in the ability of RFGs to regulate the various isoforms of known effector families. We have also identified several proteins as novel effectors of RFGs with differential binding specificities to the various RFGs. We propose that specificity among RFGs is achieved by the differential regulation of combinations of effector families as well as by the selective regulation of different isoforms within an effector family. An understanding of this new level of complexity in the signaling pathways regulated by RFGs is necessary to understand how they carry out their many cellular functions. It will also likely have critical implications in the treatment of human diseases such as cancer.