H-Ras, N-Ras, and K-Ras proteins have distinct biological properties, despite ubiquitous expression and similar affinities for regulators and effectors. C-terminal hypervariable regions that distinguish H-Ras, N-Ras, and K-Ras proteins direct them to distinct membrane compartments, where they may encounter regulators and effectors at different local concentrations. Jura and coworkers now report that these membrane-targeting domains direct differential ubiquitination of Ras proteins and so provide a molecular mechanism to explain the sorting process and, perhaps, some of the dramatic differences in biological potency among H-Ras, N-Ras, and K-Ras proteins.
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