Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Apr;23(2):145-53.
doi: 10.1016/j.semcdb.2011.09.002. Epub 2011 Sep 8.

Ras trafficking, localization and compartmentalized signalling

Ian A Prior  1 , John F Hancock
Affiliations
Review

Ras trafficking, localization and compartmentalized signalling

Ian A Prior et al. Semin Cell Dev Biol. 2012 Apr.

Abstract

Ras proteins are proto-oncogenes that are frequently mutated in human cancers. Three closely related isoforms, HRAS, KRAS and NRAS, are expressed in all cells and have overlapping but distinctive functions. Recent work has revealed how differences between the Ras isoforms in their trafficking, localization and protein-membrane orientation enable signalling specificity to be determined. We review the various strategies used to characterize compartmentalized Ras localization and signalling. Localization is an important contextual modifier of signalling networks and insights from the Ras system are of widespread relevance for researchers interested in signalling initiated from membranes.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Ras activation cycle
Ras is activated when GTP bound. Approximately 20 Ras effectors have been identified that modulate key proliferative, survival and cell migration pathways.
Figure 2
Figure 2. The Ras Hypervariable Region (HVR) determines functional difference between isoforms
Ras isoform share sequence identity at all regions regulating activation state and effector interactions. The HVR is post-translationally modified to enable membrane interactions and differential localization (key residues to enable correct localization highlighted in red). Asterixes indicate sites of oncogenic mutations at codons 12, 13 and 61.
See this image and copyright information in PMC

References

    1. Bos JL, Rehmann H, Wittinghofer A. GEFs and GAPs: critical elements in the control of small G proteins. Cell. 2007;129:865–77. - PubMed
    1. Wittinghofer A, Franken SM, Scheid ig AJ, Rensland H, Lautwein A, Pai EF, et al. Three-dimensional structure and properties of wild-type and mutant H-ras-encoded p21. Ciba Found Symp. 1993;176:6–21. discussion 21-7. - PubMed
    1. Freedman TS, Sondermann H, Friedland GD, Kortemme T, Bar-Sagi D, Marqusee S, et al. A Ras-induced conformational switch in the Ras activator Son of sevenless. Proc Natl Acad Sci U S A. 2006;103:16692–7. - PMC - PubMed
    1. Ebinu JO, Bottorff DA, Chan EY, Stang SL, Dunn RJ, Stone JC, Ras GRP. a Ras guanyl nucleotide-releasing protein with calcium-and diacylglycerol-binding motifs. Science. 1998;280:1082–6. - PubMed
    1. Mor A, Campi G, Du G, Zheng Y, Foster DA, Dustin ML, et al. The lymphocyte function-associated antigen-1 receptor costimulates plasma membrane Ras via phospholipase D2. Nat Cell Biol. 2007;9:713–9. - PubMed

Publication types