Differential modification of Ras proteins by ubiquitination

被引:159
作者
Jura, N
Scotto-Lavino, E
Sobczyk, A
Bar-Sagi, D [1 ]
机构
[1] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Grad Program Mol & Cellular Biol, Stony Brook, NY 11794 USA
[3] SUNY Stony Brook, Grad Program Mol & Cellular Pharmacol, Stony Brook, NY 11794 USA
[4] SUNY Stony Brook, Cold Spring Harbor Lab, Dept Phys, Cold Spring Harbor, NY 11724 USA
关键词
D O I
10.1016/j.molcel.2006.02.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ras proteins are essential components of signal transduction pathways that control cell proliferation, differentiation, and survival. It is well recognized that the functional versatility of Ras proteins is accomplished through their differential compartmentalization, but the mechanisms that control their spatial segregation are not fully understood. Here we show that HRas is subject to ubiquitin conjugation, whereas KRas is refractory to this modification. The membrane-anchoring domain of HRas is necessary and sufficient to direct the mono- and diubiquitination of HRas. Ubiquitin attachment to HRas stabilizes its association with endosomes and modulates its ability to activate the Raf/ MAPK signaling pathway. Therefore, differential ubiquitination of Ras proteins may control their location-specific signaling activities.
引用
收藏
页码:679 / 687
页数:9
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