Cell Biology

Turn On and Stay Put

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Science  03 Sep 2010:
Vol. 329, Issue 5996, pp. 1129
DOI: 10.1126/science.329.5996.1129-b

The Ras pathway transduces extracellular signals into intracellular gene expression profiles and regulates physiological processes such as proliferation, differentiation, and survival; defective Ras signaling can cause cancer and developmental disorders. Ras proteins are small GTPases, and their compartmentalization and controlled activation are crucial. Ras proteins are activated by guanine nucleotide exchange factors (GEFs) that put on a GTP and take away a GDP. Previous studies have shown that conjugating the small molecule ubiquitin to Ras can regulate its intracellular localization. Xu et al. have found that the GEF Rabex-5 is also an E3 ubiquitin ligase; it can attach ubiquitin to Ras in vitro, and it regulates Ras localization and activity in mammalian cells. Yan et al. have found that Rabex-5 signaling is essential in Drosophila. The loss of Rabex-5 caused gross developmental defects, including increased size and ectopic wing veins. Because Rabex-5 has both GEF and E3 ligase activity, it may serve to integrate these two regulatory pathways.

Curr. Biol. 20, 1372; 1378 (2010).

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